Born in Makó, in present-day Hungary, Pulitzer (pronounced "pull-it-sir") sought a military career, but was turned down by the Austrian army for frail health and poor eyesight. He emigrated to the United States in 1864 to serve in the American Civil War. After the war he settled in St. Louis, Missouri, where in 1868 he began working for a German-language daily newspaper, the Westliche Post. He joined the Republican Party and was elected to the Missouri State Assembly in 1869. In 1872, Pulitzer purchased the Post for $3,000. Then, in 1878, he bought the St. Louis Dispatch for $2,700 and merged the two papers, which became the St. Louis Post-Dispatch, which remains St. Louis' daily newspaper. It was at the Post-Dispatch that Pulitzer developed his role as a champion of the common man with exposès and a hard-hitting populist approach.

In 1883 Pulitzer, by then a wealthy man, purchased the New York World, a newspaper that had been losing $40,000 a year, for $346,000 from Jay Gould. Pulitzer shifted its focus to human-interest stories, scandal, and sensationalism. In 1885, he was elected to the U.S. House of Representatives, but resigned after a few months' service; it seemed that politics were not his cup of tea. In 1887, he recruited the famous investigative journalist Nellie Bly. In 1895 the World introduced the immensely popular Yellow Kid comic by Richard F. Outcault, the first newspaper comic printed with color. Under Pulitzer's leadership circulation grew from 15,000 to 600,000, making it the largest newspaper in the country.

The editor of the rival New York Sun attacked Pulitzer in print, calling him in 1890 "The Jew who abandoned his religion". After the move, intended to alienate Pulitzer's Jewish readership, Pulitzer's already failing health deteriorated rapidly, and he left the newsroom, although he continued to actively manage the paper from his vacation retreat in Bar Harbor Maine and his New York mansion.

In 1895, William Randolph Hearst purchased the rival New York Journal, which led to a circulation war. This competition with Hearst, particularly the coverage before and during the Spanish-American War, linked Pulitzer's name with yellow journalism.

After the World exposed a fraudulent payment of $40 million by the United States to the French Panama Canal Company in 1909, Pulitzer was indicted for libeling Theodore Roosevelt and J. P. Morgan. The courts dismissed the indictments, in a victory for freedom of the press.

In 1892, Pulitzer offered Columbia University's president, Seth Low, money to set up the world's first school of journalism. The university initially turned down the money, evidently unimpressed by Pulitzer's unscrupulous character. In 1902, Columbia's new president Nicholas Murray Butler was more receptive to the plan for a school and prizes, but it would not be until after Pulitzer's death that this dream would be fulfilled. Pulitzer left the university $2 million in his will, which led to the creation in 1912 of the Columbia University Graduate School of Journalism, but by then the first school of journalism had been created at the University of Missouri. Columbia's Graduate School of Journalism remains one of the most prestigious in the world.

Joseph Pulitzer died aboard his yacht in the harbor of Charleston, South Carolina in 1911. He is interred in the Woodlawn Cemetery in The Bronx, New York. In 1917, the first Pulitzer Prizes were awarded, in accordance with Pulitzer's wishes.

In 1989 Pulitzer was inducted into the St. Louis Walk of Fame.

Allen Steele wrote an altenative-history description of Pulitzer vainly trying to escape a St. Louis which is being engulfed by the Martian invasion described in H. G. Wells's The War of the Worlds. Published in the Kevin J. Anderson's anthology War of the Worlds: Global Dispatches, it depicts Pulitzer as a tragic figure, faced with the relentless advance of the Martians and regretting the arrogance of power which had led him to promote the war with Spain.