It is the largest daily newspaper in the metropolitan area by circulation, surpassing the Belleville News-Democrat, Alton Telegraph, and Edwardsville Intelligencer.

[3] The paper is owned by Lee Enterprises of Davenport, Iowa, which purchased Pulitzer, Inc. in 2005 in a cash deal valued at $1.46 billion.

On April 10, 1907, Joseph Pulitzer wrote what became known as the paper's platform: 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.

The next day, October 13, 1882, Cockerill re-ran an offensive "card" by John Glover that the paper had published the prior year (November 11, 1881).

"[citation needed] At one time, the St. Louis Post-Dispatch had the second-largest news bureau in Washington, D.C., of any newspaper in the Midwestern United States.

[12] In August 1973 a Teamsters union local representing Globe-Democrat and Post-Dispatch staffers went on strike, halting production for six weeks.

[14] The best submissions, including a duck-shaped cucumber and a woman born on December 7, 1941, with the initials W.A.R., were illustrated by Post-Dispatch artist Dan Martin and featured in the October 6, 2003, edition.

On March 23, 2009, the paper converted to a compact style every day from the previous broadsheet Sunday through Friday and tabloid on Saturday.

[23] According to a 2017 press release from Lee Enterprises, the paper reaches more than 792,600 readers each week and stltoday.com has roughly 67 million page views a month.

On February 11, 1901, the paper introduced a front-page feature called the "Weatherbird", a cartoon bird accompanying the daily weather forecast.