Adams was born Franklin Leopold Adams to Moses and Clara Schlossberg Adams in Chicago on November 15, 1881. He changed his middle name to "Pierce" when he had a Jewish confirmation ceremony at age 13. Adams graduated from the Armour Scientific Academy (now Illinois Institute of Technology) in 1899, attended the University of Michigan for one year and worked in insurance for three years.

His books include In Cupid's Court (1902), Tobogganning on Parnassus (1911), In Other Words (1912) and Answer This One (a 1927 trivia book with Harry Hansen). The two-volume The Diary of Our Own Samuel Pepys, collected from his newspaper columns, was published in 1935 by Simon and Schuster. The Melancholy Lute (1936) featured Adams' selections from three decades of his work.

Signing on with the Chicago Journal in 1903, he wrote a Sports column and then a humor column, "A Little about Everything". The following year he moved to the New York Evening Mail, where he worked from 1904 to 1913 and began his column, then called "Always in Good Humor", which used reader contributions.

During his time on the Evening Mail, Adams wrote what remains his best known work, the poem Baseball's Sad Lexicon, a tribute to the Chicago Cubs double play combination of "Tinker to Evers to Chance". In 1911, he added a second column, a parody of Samuel Pepys's Diary, with notes drawn from F.P.A.'s personal experiences. In 1914, he moved his column to the New-York Tribune, where it was famously retitled The Conning Tower and was considered to be "the pinnacle of Verbal wit".

During World War I, Adams was in the U.S. Army, serving in military intelligence and also writing a column, "The Listening Post", for Stars and Stripes Editor Harold Ross. After the war, the so-called "comma-hunter of Park Row" (for his knowledge of the language) returned to New York and the Tribune. He moved to the New York World in 1922, and his column appeared there until the paper merged with the inferior New York Telegram in 1931. He returned to his old paper, by then called the New York Herald Tribune, until 1937, and finally moved to the New York Post, where he ended his column in September 1941.

During its long run, "The Conning Tower" featured contributions from such Writers as Robert Benchley, Edna Ferber, Moss Hart, George S. Kaufman, Edna St. Vincent Millay, John O'Hara, Dorothy Parker and Deems Taylor. Having one's work published in "The Conning Tower" was enough to launch a career, as in the case of Dorothy Parker and James Thurber. Parker quipped, "He raised me from a couplet." Parker dedicated her 1936 publication of collected poems, Not So Deep as a Well, to F.P.A. Many of the poems in that collection were originally published in "The Conning Tower".

As a panelist on radio's Information Please (1938–48), Franklin P. Adams was the designated expert on poetry, old barroom songs and Gilbert and Sullivan, which he always referred to as Sullivan and Gilbert. A running joke on the show was that his stock answer for quotes that he didn't know was that Shakespeare was the author. (Perhaps that was a running gag: Information Please's creator/producer Dan Golenpaul auditioned Adams for the job with a series of sample questions, starting with: "Who was the Merchant of Venice?" Adams: "Antonio." Golenpaul: "Most people would say 'Shylock.'" Adams: "Not in my circle.") John Kieran was the real Shakespearean expert and could quote from his works at length.

Adams is credited with coining the term "aptronym" for last names that fit a person's career or job title, although it was later refined to "aptonym" by Frank Nuessel in 1992.

Adams was portrayed by the actor Chip Zien in the film Mrs. Parker and the Vicious Circle (1994).

Much later, the Writer E. B. White freely admitted his sense of awe: "I used to walk quickly past the house in West 13th Street between Sixth and Seventh where F.P.A. lived, and the block seemed to tremble under my feet—the way Park Avenue trembles when a train leaves Grand Central."