Key & Peele was created by Keegan-Michael Key and Jordan Peele, who had both previously worked together on Mad TV before developing their own show for Comedy Central.

The show was first announced by Comedy Central in June 2011, and Key and Peele launched a supporting web series ahead of the premiere in January 2012.

The recurring East/West Bowl sketch was inspired by Jordan Peele discovering a real football player named D'Brickashaw Ferguson while playing the video game Madden NFL.

In the show's final episode, the recurring Mojave Desert car-ride segments are revealed to be an extension of 'I Said Bitch,' the very first sketch from the show's premiere episode, bringing the series full circle.

In the third edition of the East/West Bowl sketch, real football players with unusual names, including Ha Ha Clinton-Dix, Ishmaa'ily Kitchen, and D'Brickashaw Ferguson himself, appeared alongside the fictional characters.

According to Key, real NFL player Aaron Rodgers improvised his own punchline when he appeared in the East/West Bowl sketch as 'A. A. Ron Rodgers,' a reference to the Mr. Garvey sketches.

President Barack Obama publicly praised the 'Luther, his Anger Translator' sketch during an interview on Late Night with Jimmy Fallon in April 2012, calling it 'pretty good stuff.'

Keegan-Michael Key reprised his Luther character live at the White House Correspondents' Dinner in 2015, acting as anger translator for the real President Obama.

Dave Chappelle accused Key & Peele of copying the sketch format he originated with Chappelle's Show, though he stated he remained a fan of the series.

In 2024, a moment of the real Barack Obama shaking hands with white athletes but hugging Black athletes at a USA Basketball event went viral for resembling a 2014 Key & Peele sketch depicting the same behavior from Peele's Obama character.

Key and Peele reprised their comedic duo dynamic in other projects, including playing FBI agents in the first season of Fargo, dueling as historical figures in Epic Rap Battles of History, voicing carnival toys in Toy Story 4, and starring in the film Keanu, which they also produced.