John's two older brothers died in infancy. Three of his younger brothers did not marry while the fourth, Benjamin Wickham, married and had three sons who died unmarried. John entered the Royal Naval College in February, 1812. In 1815, he became an Admiralty Midshipman and was posted to HMS Nightingale and in 1818 to HMS Hyperion. In 1819, he passed his Lieutenant's examination. John was commissioned Lieutenant in 1827 and posted to HMS Adventure, a surveying vessel commanded by Captain Phillip Parker King that charted the coasts of Peru, Chile and Patagonia. In company with HMS Adventure was the smaller HMS Beagle, a ten gun sloop on her first survey expedition.

In June 1831, John was commissioned First Lieutenant and appointed as second-in-command of the HMS Beagle during her second survey mission, which circumnavigated the Earth from December 27, 1831 to October 2, 1836. The passengers included the young and unpaid naturalist Charles Darwin, who became John's good friend and cabin-mate. Darwin, who was more than ten years younger than John, wrote, "Wickham is a glorious fellow. By far the most conversible person on board. There is not another on the ship worth half of him." John playfully nicknamed Darwin the "Fly Catcher" due to his numerous insect specimens that littered their craft. During the voyage, John also served as an illustrator, completing a number of competent sketches (see his drawing of the HMS Beagle). While visiting Chile in 1835, a massive earthquake estimated as magnitude 8.5 (followed by three tsunamis) leveled the city of Concepcion, and John sketched the city's destroyed cathedral shortly thereafter (see drawing). Their survey mission became the subject of Darwin's 1839 book The Voyage of the Beagle.

In 1837, John was promoted to Captain of the Beagle and commanded her during her third voyage, which did not include Darwin. During this voyage, the crew conducted various maritime expeditions and hydrographic surveys along the Australian coastline. While exploring the northern coast of Australia in 1839, John named Port Darwin after his not-yet-famous associate, who was still 20 years from publishing his seminal book On the Origin of Species. By 2010, Darwin had grown to be a city of more than 125,000 people, and serves as the capital of the Northern Territory (see picture).

Due to poor health after a bout with dysentery, John resigned his command of the Beagle in March, 1841. He reported back to London, published his survey maps, and retired from the Royal Navy, then moved back to Australia in 1842 to get ready for his impending marriage. On October 27, 1842 John married Anna Mcarthur in Parramatta, New South Wales (see her picture). They had three children together: Charles, Ellen, and Alfred. Anna was the second of six daughters of Hannibal Hawkins Macarthur, a politically connected businessman who was chairman of directors of the Bank of Australia. Anna died from a painful illness in Sydney on June 23, 1852, and John remarried on October 1, 1857 to Irish immigrant Ellen Deering of Ipswich, who bore him two sons (see Ellen's picture).

On November 14, 1842, Governor Sir George Gipps appointed John to be the first Police Magistrate of Brisbane. In January 1843, John and his wife of three months arrived on the paddle-wheel steamship Shamrock in Brisbane Town, which then had a population of only 812 people (see John then). The penal colony era of Moreton Bay District (now Brisbane) was over and the region was opened to free settlement in 1840, but the area was still a wild frontier. The local population consisted largely of white ex-convicts and Aborigines, many of whom were hostile to whites and fond of spearing them. John served as Police Magistrate of the Moreton Bay District from 1842 until 1857 then became Government Resident from 1853 to 1859. During this time, he was the senior government figure in the region and charged "with the general interest of government within Moreton Bay and to be the representative of the Governor within its limits." John, known as His Worship in those days, took a hands-on approach to carrying out his duties. For example, in 1846 when Mrs. Gage of Breakfast Creek was being robbed and violated by a man threatening to cut her throat with a knife, John rode to the scene, chased down the suspect, and apprehended him.

John lived in the Newstead House, the oldest existing house in Brisbane. He bought the property in 1847 from his brother-in-law, Patrick Leslie, a pioneering pastoralist. John expanded the two-story Colonial Georgian cottage into a sprawling homestead by adding additional rooms, as well as a slate roof and stone foundations (see picture). It overlooks the Brisbane River and served as a center of social activity and an unofficial Government House during this time. On November 2, 1849 Anna's youngest child Alfred William Wickham was born at Newstead; and on November 25, 1858, Ellen gave birth to John Harold Wickham there. Decades later, the house became a museum and headquarters for the Historical Society of Queensland, except during World War II, when it was used by the American military. The present-day Brisbane suburb of Newstead resulted from the estate being subdivided around 1878. In 1933, a brass plaque honoring John's residency at Newstead was provided by his grandson and affixed to the house (see plaque).

During the separation of the new colony of Queensland from New South Wales in 1859, John was offered the post of colonial treasurer in the new administration, but declined the position due to election costs. On February 2, 1860, he and his family left Australia for Britain aboard the Duncan Dunbar, even though Ellen was heavily pregnant. Before leaving, John donated a Galapagos tortoise named Harriet (and two other tortoises) to the Brisbane Botanic Gardens that he had been keeping on the Newstead estate. Harriet gained fame for her longevity, living 175 years until 2006 (see her picture). Darwin (or one of his shipmates from the HMS Beagle) had collected Harriet in 1835 while she was still a plate-sized juvenile, but the foggy climate in England was not salubrious for her, so John was tasked with taking her to Australia. Clueless zookeepers initially believed that Harriet was a male and unsuccessfully tried for about 125 years to mate her with other female tortoises (until a visiting American herpetologist spotted the difficulty). Despite this, the good natured reptile enjoyed being patted by humans and munching on hibiscus flowers. While some skeptics have questioned Harriet's lightly documented past, DNA tests proved her age and Darwin wrote a letter in 1860 confirming that John had taken possession of the surviving tortoises from the HMS Beagle.

John's son Henry Falkland Wickham was born at sea near the Falkland Islands on March 11, 1860 during the voyage back to Britain. Henry's middle name was derived from these islands. After returning to Britain, John visited his younger brother Benjamin, Paymaster-in-Chief of the Royal Navy, at Elgin in Scotland. Along with two other former HMS Beagle shipmates, John had a brief reunion with an ailing but now famous Darwin at Down House in Kent in October, 1862. (Darwin recovered and lived another twenty years). John retired to southern France, where he died from a stroke on January 6, 1864 and was buried at St. Martins Church cemetery in the luxurious seaside resort of Biarritz on the Bay of Biscay (see his grave). Ellen soon sold Newstead for 4,000 pounds and eventually returned to Australia, where she died at Sandgate, Queensland on November 9, 1896. Most of John's letters and other papers were destroyed by a fire in 1874.

In the spirit of John's peripatetic career, his children lived around the globe. Charles Brenton Wickham, the eldest son, was educated in Australia before embarking on a military career in England. At the age of eighteen he entered the Royal Military Academy at Woolwich in London, afterwards rising to the rank of Colonel in the Royal Horse Artillery. He married Eleanora Mary Davie Wynch in 1881 and died on August 1, 1908 at Ealing, Middlesex, England. John's only daughter Ellen Susan Wickham was placed in the care of an aunt and uncle after the early death of her mother Anna. They moved back to Britain, taking Ellen with them, and she never returned to Australia. She married Admiral Henry Wandesford Comber, R.N. in 1875 and died in 1933 in England. Alfred William Wickham, the second son, married Isabel Irene Fernandez in 1877 and settled in Montevideo, Uruguay, where he lived until his death in about 1924. The third son, John Harold Wickham, died at age ten from an undisclosed illness while traveling in the Black Forest region of Germany. The fourth son, Henry Falkland Wickham, worked as a journalist in Sydney, Australia. He married Elizabeth Mary Josephine "Lizzie" Keegan in 1889 and died in Australia in 1936 after a 45-year marriage that produced three daughters.

In Brisbane, Wickham Terrace and Wickham Street are named in John's honor. The Wickham River and Wickham Point in the Northern Territory are also named after him, as is the mining town of Wickham in Western Australia. Also named for John is Cape Wickham, on the northern tip of King Island off the coast of Melbourne, which was explored by him in 1838. Besides being the brand name of a popular Australian brie with a superb rich flavor, Cape Wickham is the site of a famous 52-meter lighthouse (see lighthouse) that is the tallest in the southern hemisphere and marks the entrance to the perilous Bass Strait. There are also two islands named for him off the coast of Australia, one off the coast of Chile, and one in the Solomon Islands. There are three Mount Wickhams, two in Australia and one in the Falkland Islands, that commemorate him. Lastly, there is Wickham's Grevillea (Grevillea wickhamii), an Australian shrub with holly-like leaves that grows to a height of 18 feet (see shrub)