[1] The building that houses Pete's was built in 1829, and was originally the Portman Hotel;[2] liquor may have been sold there as early as 1851[3] or 1852[4] – when it was a "grocery & grog" store[3] – and the first official drinking establishment founded by 1864.

[3][4] The writer O. Henry lived down the street at 55 Irving Place from 1903 to 1907,[4] and Healy's appears in his short story "The Lost Blend" under the name "Kenealy's".

[4] Local legend also has it that he wrote his well-known story "The Gift of the Magi" in Healy's second booth from the front, but this appears to be apocryphal.

Pete's Tavern has appeared in numerous films and television programs, including Two for the Seesaw, Seinfeld, Ragtime, Endless Love, Law & Order, Nurse Jackie, Spin City, Sex and the City, Across the Sea of Time, The Guru, Blue Bloods, The Blacklist, and more recently, Fleishman is in Trouble.

It has also been used as a location for television commercials such as Miller Lite ads with Ben Davidson and Tony Esposito, as well as print advertisements.