John's great-great grandfather Thomas Wickham, a Puritan settler, had emigrated to Wethersfield, Connecticut in about 1648 from England. Thomas' son Joseph made the move to Long Island a generation later and by John's time the Wickhams were known as one of the more prominent families in the area. Notable ancestors on his mother's side include Clement Fanning, the Norman-Irish mayor of Limerick in 1557, and Richard "Bull" Smith, the pugnacious English settler who achieved great success as the original patentee of Smithtown on Long Island after a long and controversial legal struggle. Richard received his moniker because he preferred riding his tame bull named "Whisper" rather than a horse. As the fanciful story goes, he had an agreement with the Nesaquake Indians, circa 1665, that he could have as much land as he could encircle in one day riding on the back of his bull. Rising early on the morning of the longest day of the year, Richard was able to define a vast domain that made him one of the wealthiest men on Long Island. A 14-foot-tall, 5-ton bronze statue of a bull crafted by noted sculptor Charles Rumsey was unveiled at a prominent intersection of the village of Smithtown on May 10, 1941 to commemorate Richard's reputed exploit (see picture).

During the American Revolution, John supported the Loyalist cause and was commissioned as an ensign on May 10, 1781 in the famed King's American Regiment, which was raised by his uncle Edmund Fanning. He also studied at the Military School at Arras, France. Later during the course of the war, John was traveling by foot from New York to Charleston, South Carolina to meet up with his uncle Edmund, who was then a commander of British troops there (see letter from John to his uncle). Edmund, who took a special interest in developing John's career, had promised to send him on to England to be further educated, but John was detained at a crossing at Hicksford, Virginia and found to be carrying papers that implicated him as a spy. A court martial followed, where a certain Colonel Robert Goode of Whitby, who was presiding over the affair, became impressed by John's character and urged a respite. John was sequestered in Williamsburg for the rest of the war and studied law at William and Mary. As might be expected, John was extremely grateful to those who came to his aid and protection during his court martial, and in the years that followed, always made sure these people were substantially cared for. In 1785, he began to practice law in Williamsburg and then moved to Richmond in 1790 after it was named the new state capital. He quickly built a successful practice by helping British merchants collect debts owed by Americans who had become financially strapped by the war effort. On December 24, 1791, he married in Brunswick his first cousin, sixteen-year-old Mary Smith Fanning, who was the only child of William Fanning and Mary Gray, although she had a half-brother named Henry, from her widowed mother's previous marriage to Littleton Tazewell, who became President Pro Tempore of the U.S. Senate. Before her death in 1799, Mary bore John two sons who would go on to marry two sisters from the wealthy Carter family. John was remarried in March of the next year to Elizabeth Seldon McClurg, daughter of Richmond's mayor and soon-to-be mother of seventeen more of his children (thirteen of Elizabeth's children lived to adulthood). One of his grandsons from his first marriage, Williams Carter Wickham, would become a prominent Confederate general, while a granddaughter from his second marriage, Charlotte Wickham, would marry Rooney Lee, the second son of General Robert E. Lee. There have been many other notable kin, including his nephew William Wickham, a political leader residing in John's hometown of Cutchogue on Long Island, and Elinor Wickham, a descendant in St. Louis who married publishing heir Joseph Pulitzer II.

Despite his military service for the Loyalist cause, John was readily accepted into Virginia society. In fact, one of his closest professional associates was his neighbor John Marshall, who besides serving with Washington at Valley Forge and being a second cousin of Thomas Jefferson, was also fourth Chief Justice of the Supreme Court, earning the nickname "The Great Justice" for his incisive opinions which helped define the role of the Supreme Court in American life. Frequently they could be found together at the Buchanan Spring Quoits Club, socializing with other prominent citizens such as John Buchanan and John D. Blair. However, given his Loyalist past and his family's setbacks because of their political views (his uncle Parker Wickham was banished from New York), John was careful to steer clear of public office, although he did participate in the effort to build Monumental Church (see picture) as a tribute to the 72 people (including Virginia's governor) who died in the horrific Richmond Theater fire that occured on Christmas Eve, 1811. In that fire, John's eldest daughter Julia was almost killed, but she was pulled by her hair from the inferno to safety outside. Completed in 1814, the church is the only surviving example of a Robert Mills octagonal auditorium in the Classical style.

After his second marriage, John became known as a staunch Federalist in the same spirit as his father-in-law, Dr. James McClurg (1746-1823), a member of the convention which framed the Constitution of the United States in 1787. At the Constitutional Convention, James advocated a life tenure for the President and argued for the ability of the federal government to override state laws, but left the convention early and did not sign the Constitution. James (see picture) was born near Hampton, VA and was a graduate of the College of William and Mary and the University of Edinburgh. He completed postgraduate medical studies in Paris and London and published Experiments upon the Human Bile and Reflections on the Biliary Secretions in 1772, which was well received and translated into several languages. During the American Revolution, he served as physician-general and director of hospitals for Virginia. In 1779, he was appointed professor of anatomy and medicine at the College of William and Mary, but the chair was discontinued in 1783, so he moved to Richmond, where he became mayor in 1797. U.S. Senator Benjamin Watkins Leigh, a widely published political writer married to John's daughter Julia, was another conservative in John's extended family, known for his strong belief that voting was not a right and that only a person owning at least fifty acres of land was entitled to representation.

In 1807, John was the lead counsel for Vice President Aaron Burr in his trial for treason, one of the most sensational court cases in American history. Burr, who once said that "great souls care little for small morals," had already been indicted for the murder of Alexander Hamilton (1755-1804), but now he faced charges of treason for attempting to conquer western regions of the United States and Mexico with the help of Great Britain. Among the most brilliant men of his time, Burr, whose father co-founded Princeton University, reached the post of Vice President under Jefferson in 1800, but after killing Hamilton in a duel, his political career went into a permanent decline. Disgruntled, he headed West and plotted to regain his status through conquering his own empire, but was soon arrested and brought to Richmond for trial. John was assisted in the case by two of the most eminent attorneys of his day: Edmund Randolph and Luther Martin. The trial was presided over by John's close associate, John Marshall, who besides serving as Chief Justice of the Supreme Court was also a circuit court judge in Richmond. In a famous incident occurring at the time of the trial, Marshall stopped by John's house for a dinner party, not realizing that another one of the guests was Burr. Despite President Jefferson's personal involvement on behalf of the prosecution, Burr was acquitted after the court followed a strict reading of the Constitution and excluded all evidence not directly related to the act of treason. Legend has it that John invited Marshall over for a game of chess the night before the verdict was rendered and during the course of the game they decided the outcome of the case. The prosecutor for the case, William Wirt, who later became a presidential candidate, noted that John was "distinguished by a quickness of look, a sprightly step,... and a wit, whose vivid and brilliant coruscations can gild and decorate the darkest subject." An outfoxed Jefferson, who personally knew John, had a dimmer view, claiming that Burr had escaped execution due to "tricks of the judges" and that the case showed that there was an "error in our Constitution, which makes any branch independent of the nation." After his acquittal, Burr was shunned by society, so he went to Europe for several years before returning to New York in 1812 where he practiced law and lived in relative obscurity.

After the trial, Burr’s associate General James Wilkinson challenged John to a duel, claiming that his reputation had been tarnished by John’s comments during the case. John politely declined, suggesting instead that they settle their differences in the courtroom. Wilkinson’s concern for his reputation is a bit odd, considering that besides being an officer in the U.S. Army he was also secretly working as a double-agent for the Spanish government. Wilkinson’s military career came to an inglorious end during the War of 1812, when his force of 4,000 men was defeated by about 100 enemy troops during a catastrophic invasion of Canada. Meanwhile, in 1810 John would tangle with Jefferson in another legal squabble involving the riparian rights of alluvial land claimed by New Orleans attorney Edward Livingston, who was a member of the famous New York family of Livingston Manor. Livingston filed a civil lawsuit against Jefferson for $100,000, then a considerable sum considering that Jefferson’s 10,000 acres of land and 200 slaves were worth only $200,000. Jefferson attempted to secure John’s services, but John opted to represent Livingston instead. The suit was dismissed due to lack of jurisdiction, although Livingston eventually secured his property rights, then went on to become a U.S. Senator from Louisiana and served as Secretary of State under President Andrew Jackson. The case's dismissal was a welcome relief for Jefferson, whose benighted financial affairs once caused John to dryly remark: "Mr. Jefferson's reputation does not rest on his knowledge of agriculture."

When he wasn't in the courtroom, John frequently pursued his passion for horse breeding, his most important success being Boston, (see picture), considered America's first great race horse. Named for the card game, not the city, Boston was the temperamental grandson of Sir Archy and foaled in Virginia in 1833. As a colt, he liked to roll on his riders, so trainer John Belcher and some stable hands had to cure the problem by sitting on his head and beating him with sticks. In his first race, he was way ahead when he stopped dead and refused to budge, but he won the final two races of his three-year-old season and didn't lose again for several years. Belcher interested horse racing titan Colonel W.R. Johnson in purchasing Boston in a memorable demonstration where the horse was raced against two others. Boston was lagging way behind and appeared to be defeated, but as his trainer turned away in disgust, Boston suddenly blew past his competitors and easily won the race. Under Johnson, Boston won an unbroken stream of victories to the point that other owners refused to race their horses against him, but in September of 1841, Boston experienced his third career loss to Fashion, a filly half his age. Johnson immediately challenged her to a rematch the next spring, setting up one of the most famous horse racing events in history. The event, held at New York's Union Course, led to riots when hordes of fans overwhelmed New York City's railway system vainly trying to reach the heavily hyped competition, which Boston lost after sustaining an injury. After winning the final race of his career at age ten, he was relocated to Kentucky, where he was finally bred to some quality mares. In the months before his death in January of 1850, despite being blind and unable stand on his own, he sired his two finest sons, Lexington and Lecomte. While Lecomte's promising career was cut short by an early death, Lexington went on to become the champion of his era and the greatest sire of the last half of the 19th century. His skeleton can be seen at the Smithsonian Institution in Washington D.C. at the Hall of Mammals.

In 1812, John completed what is now known as the Wickham House (see front, back), a grand neoclassical home that is considered one of the finest examples of architecture from the Federal period. Sometimes called the Wickham-Valentine House, this National Historic Landmark was designed by Massachusetts architect Alexander Parris (1780-1852), designer of Virginia's Governor's mansion and Boston's Faneuil Hall. John, who intended for his spendid home to represent his outstanding wealth and reputation, was one of relatively few Americans to be building grand homes during this time, because the country was still making a slow recovery from the effects of the American Revolution. Perhaps best known for its magnificent elliptical staircase (see picture), the residence also features extraordinary neoclassical wallpaintings with ancient Greek, Roman and Egyptian themes. Recently restored, the house is open to the public and is part of the Valentine Museum complex, located at 1015 East Clay Street in downtown Richmond, in a neighborhood called Court End, an area developed around the state and federal courts where many of the city's elite lived at the time. Originally, the estate grounds of John's home consisted of approximately a city block with many outbuildings, including a detached kitchen, stables, and a separate home called Harvie House for his numerous children, but as the city grew, much of the property was sold off and redeveloped.

John's widow Elizabeth continued to live in the Wickham House with two of her daughters until her death in 1853, when the property was sold by the Wickham family to James P. Ballard. The Valentine Museum, which currently owns the Wickham House, was established in 1892 through the will of Mann S. Valentine II, a Richmond entrepreneur who purchased the Wickham House in 1882. Valentine had started the Valentine Meat Juice Company in the 1870s to produce a healthful drink for his ailing wife. The product, extracted from beef marrow, found a worldwide market, enabling him to leave $50,000 and an eclectic collection of books, manuscripts, Indian artifacts and other Virginiana items, plus his family home, for a museum. By 1924, the Valentine had acquired and was using most of the buildings in the 1000 block of East Clay. After closing for a few years, the museum reopened in 1930 under the leadership of Edward V. Valentine, the founder's brother and a prominent sculptor, and other Valentine kin. Once a "Smithsonian of the South," the museum today focuses on interpreting Richmond's life and history, including the accomplishments of several generations of Wickhams.