The duo was formed in 2007 in Los Angeles after Lindhome and Micucci met during an improv show at the Upright Citizens Brigade Theatre.

[3] Years later, both of them separately moved to Los Angeles, with Lindhome pursuing an acting career and Micucci coming after college with plans to design puppets.

They met each other again in the lobby at the Upright Citizens Brigade Theatre in Los Angeles during a Doug Benson show, where the two were both "on bad dates" and recognized each other from commercial auditions.

[6] Garfunkel and Oates was formed when they started working together to adapt Imaginary Larry (2009), a short film written by Lindhome during the 2007–08 Writers Guild of America strike, into a musical.

[7][8] Lindhome posted a video of the duo performing to YouTube in 2007 for her friends and family to watch, which soon appeared on the website's home page.

[9] After their song "Fuck You" became popular on YouTube in 2009, Garfunkel and Oates earned a large following online and decided to start performing professionally.

[10][5] In early 2009, they started the Garfunkel and Oates Hour, a monthly live show that became popular at the Upright Citizens Brigade Theater.

[20] In September 2014, IFC approved Garfunkel and Oates, a TV sitcom directed by Fred Savage and starring the duo as fictionalized versions of themselves navigating the Los Angeles comedy scene.

Former First Lady of the United States Michelle Obama, the show's star and executive producer, heard the demo and chose them to write the music for the series.

[2] In August 2021, the duo wrote a musical number for Lindhome's character Kimberly on an episode of the animated sitcom series Duncanville, "Off with the Braces".

[4][24][5][42] In 2009, Rebecca Dana of The Wall Street Journal wrote that Garfunkel and Oates were "fast becoming the darlings of the Los Angeles comedy scene...with their pretty-girl, dirty-mouth act".

[43] The Daily Dot's Audra Schroeder called them "a Swiss Army knife, at a time when artists often have to be many things to stay afloat".

[41] For Vulture, Joe Berkowitz wrote that the songs "are filled with sharp observations and hilarious stories that are distinctly feminine and quirky", adding, "The blunt, detail-packed way they rebuke potential suitors or reveal embarrassing personal insights seems brutally honest.

[44] Paste's Hudson Hongo named Micucci and Lindhome two of the best comedians of 2014 for their work as Garfunkel and Oates, while the two were included on Cosmopolitan's list of "13 Funny Women to Watch in 2014" in 2014.