The movie was filmed over a span of four years. Production took so long because filming had to be done around the actors' busy schedules. The segment with Kate Winslet and Hugh Jackman was the first to be filmed, and producer Charles B. Wessler used it to secure the financing for the rest of the movie. He called in a lot of favors to get as many high-profile actors as possible for the other short films, most of them willing to work for a few days on something unconventional. However, almost none of the actors knew completely what the other segments were about, or how the full movie would be. When it came out, none of the major actors wanted to promote it.
George Clooney turned down a cameo as himself, in a segment where he would be shown to be bad at picking up women. His response, reportedly, was "no fucking way."
Anton Yelchin originally played a necrophiliac, in a segment called The Apprentice (2014), directed by Steve Baker and Damon Escott. Another segment called "Find Our Daughter", directed by Bob Odenkirk, revolved around Julianne Moore and Tony Shalhoub being interviewed by a detective about their missing daughter. Both were removed on studio orders following a test screening, due to the highly offensive subject matter. Find Our Daughter was included on the DVD as a deleted scene, whereas The Apprentice premiered separately at the 2014 LA Comedy Festival.
Trey Parker and Matt Stone were initially set to direct a segment, but they dropped out for disliking the script.