The pilot episode was written by creator David Caspe and directed by Anthony Russo and Joe Russo, who also served as executive producers alongside Jamie Tarses and Jonathan Groff.

The cast was assembled gradually starting in February 2010, with Damon Wayans Jr. cast first as Brad, followed by Casey Wilson as Penny, then Eliza Coupe and Adam Pally, then Elisha Cuthbert, with Zachary Knighton being the last actor cast, taking on the role of Dave.

The sixth aired episode of season one, 'Of Mice and Jazz-Kwon-Do,' was taped before the death of Osama bin Laden but included a joke referencing 'bin Laden,' prompting ABC to mute the line and cut it from online streams after his death, though it remained intact on Canadian broadcasts and the DVD release.

An episode titled 'You've Got Male' originally featured a kiss between Max and a character named Ian, shown in promotional images, but the kiss was ultimately cut before airing; creator David Caspe stated this was a purely creative decision with no network pressure involved.

Vulture called ABC's erratic scheduling of the third season, combined with its lower ratings and subsequent cancellation, one of the 'worst TV decisions' of the 2012–13 television season.

After ABC canceled the show in 2013, Sony TV attempted for weeks to shop it to other networks and platforms including USA, Amazon, Netflix, TBS, and NBC, but no deal was reached and the series was officially declared ended on June 28, 2013.

In early 2015, the show's writers' room Twitter account posted a countdown clock and cryptic references (like a Natalie Imbruglia video and 'Four Seasons' hints) that fueled fan speculation of a revival, which was ultimately revealed on April 1, 2015, to have been a 55-day April Fools' prank orchestrated by a writer's assistant without Caspe's knowledge.

The cast reunited in October 2016 for a live table read at Entertainment Weekly's PopFest of a newly written 'lost' episode called 'Happy to Be Here,' which was initially teased on Twitter as an unused original script before being revealed to be brand new material.

Creator David Caspe's later NBC sitcom Marry Me is implied to share a universe with Happy Endings, as both are set in Chicago and feature the recurring character Derrick, played by Stephen Guarino, in both shows.