Nellie's parents, Ed and Emily, were married on May 5, 1881 in St. Louis. The couple had three daughters: Emily, Frances and Nellie, who was educated at Dobbs Ferry. The family lived at No. 28 Vandeventer Place, in a luxurious gated community considered at the time to be the finest neighborhood in St. Louis (see house), then the nation's fourth largest city. Their large and handsome home, built in 1892, was staffed with three servants, but seemed almost spartan compared to the colossal Catlin mansion down the street. The community was the site of numerous other mansions, but the entire neighborhood was torn down in the 1940s to make way for a VA hospital, causing it to become one of the worst neighborhoods in the city, with astronomical poverty and crime rates.

For many years, the Catlins operated a 400-employee tobacco plant in St. Louis, but with the merger of Catlin Tobacco Co. with American Tobacco Co. in 1898, they had a lot of time and money on their hands, so they began to focus on civic affairs. In 1901, Nellie's eldest sister Emily Catlin Wickham was chosen from among the debutantes by the Veiled Prophet Organization, a secret society of St. Louis' elite, to be the Queen of Love and Beauty. The socially exclusive Veiled Prophet tradition in St. Louis was the means by which young women made their formal entrance into society. A few years later, Nellie was maid of honor at the Queen of the Veiled Prophet's ball and the following April it was announced that she was engaged to Joseph Pulitzer II (JPII), the second son of newspaper publishing magnate Joseph Pulitzer I (JPI), owner of the New York World and St. Louis Post-Dispatch. JPII had spent about three years in St. Louis working for his father's newspaper and reconnected with Nellie's family, who were among the first to befriend his father when he arrived in St. Louis as an unknown immigrant from Hungary many years earlier, long before he moved on to New York City and became a media legend. Though JPII hated the sound of the name "Nellie", he soon found her to be irresistibly attractive.

With JPI's strong approval, Nellie married JPII on June 1, 1910 at the Wickham home in St. Louis (see the groom). (The groom's Jewish ancestry apparently precluded marriage in a church). Her chronically ill father-in-law was not feeling well enough to attend, but gave the couple a $50,000 solid gold dinner service, writing that "I hope there will be as little as possible in the papers about the wedding and no publicity of presents," but his extravagant gift was immediately and widely reported. Nellie received a cluster of diamonds from the groom that she wore on her dress and was given away by her uncle Daniel Catlin, Jr. since her father had passed away in 1908. Not reported in the papers was that JPI modified his will to include a $250,000 bequest to Nellie.

After a three-month European honeymoon, the newlyweds stopped by New York City, where Nellie finally met her new father-in-law. Then they returned to St. Louis and rented a three-story brick house for $100 per month at 3836 Lindell Boulevard, in one of the city's poshest areas. A few years later, they moved to Lone Tree Farm, a 100-acre estate in St. Louis County adjacent to the St. Louis Country Club, where the family dog tormented golfers by retrieving balls from the green. During the summers, they headed to Chatwold, their enormous cottage in Bar Harbor, Maine. They had three children together: Joseph, Kate and Elinor.

After the death of his father on October 29, 1911, JPII became the head of the St. Louis Post-Dispatch, the city's leading newspaper. In November 1918, he was commissioned an ensign in the United States Naval Aviation Corps. With the sale of the New York World in 1931, JPII secured his spot as the most prominent Pulitzer of his generation.

The St. Louis Post-Dispatch was a liberal paper that operated according to what was known as the Pulitzer platform, penned by JPI on April 10, 1907:

I know that my retirement will make no difference in its cardinal principles, that it will always fight for progress and reform, never tolerate injustice or corruption, always fight demagogues of all parties, never belong to any party, always oppose privileged classes and public plunderers, never lack sympathy with the poor, always remain devoted to the public welfare, never be satisfied with merely printing news, always be drastically independent, never be afraid to attack wrong, whether by predatory plutocracy or predatory poverty.

Nellie was killed in a car accident in New York City in 1925. Her oldest child, Joe (JPIII), was only eleven then, so she missed seeing her children's interesting careers and marriages (see JPIII at age 12). JPIII graduated from Harvard in 1936 and was publisher of the St. Louis Post-Dispatch for 38 years and for 31 years he chaired the board at Columbia University which awarded the coveted Pulitzer Prize established by his grandfather to recognize excellence in journalism. He expanded the family company into television, and was also an important collector of modern art who gave generously to the Harvard Art Museum.

The middle child Kate married first Captain Henry Ware Putnam, a B-29 pilot who was killed in action during World War II over Tokyo, Japan in May 1945, while she was pregnant with their second daughter. Her second husband was luckier and survived eight plane crashes. He was Air Force lieutenant general Elwood R. "Pete" Quesada (see him), who pioneered the tactical use of aircraft to support infantry. He flew 90 combat missions as a fighter pilot during World War II, including piloting Supreme Allied Commander Eisenhower on a scouting mission behind enemy lines during the Normandy invasion. Later he was the first director of the FAA, and among his mandates was that pilots were no longer allowed to walk down the passenger aisle while their plane was in flight.