Falchuk grew up in Newton, Massachusetts. His mother is Nancy Falchuk, the national president of the American Jewish women's organization Hadassah (as of 2007). He attended Beaver Country Day School. In high school, he tried to stand out from his classmates by wearing a tie to school each day and declaring himself a Republican. He said: "I was always trying to look smart because I didn't feel smart"; he actually suffered from undiagnosed dyslexia. In high school, he played baseball, basketball and lacrosse. He later attended the American Film Institute. He graduated from Hobart and William Smith Colleges in 1993. Falchuk was the commencement speaker for Hobart and William Smith Colleges' 2014 graduating classes.
Falchuk's career in television began as a writer for Mutant X (2001), Earth: Final Conflict (2001–02) and Veritas: The Quest (2003), before he was hired to work on the first season of Nip/Tuck in 2003. While working on Nip/Tuck, he formed a close bond and partnership with the show's creator, Ryan Murphy. Falchuk and Murphy went on to write a television pilot titled Pretty/Handsome, about a transsexual gynecologist, which the FX network bought in 2008. However, the pilot was not picked up as a series. As Nip/Tuck neared its sixth and final season, Falchuk and Murphy began to look for their next project, and decided to focus on a lighter subject. They teamed up with Ian Brennan, who had written a screenplay about high school show choirs, to pitch a one-hour comedy about a glee club to the Fox Broadcasting Company. Their pitch was successful and turned into the television show Glee, which premiered in 2009. Falchuk, Murphy and Brennan received two Writers Guild of America Award nominations for Best Comedy Series and Best New Series. After the early success of Glee, Falchuk signed a two-year, seven-figure deal with 20th Century Fox Television which involved further work on Glee as well as the development of other projects for the studio. Glee concluded following its sixth season, which aired from January 9 to March 20, 2015.
In 2011, Falchuk co-created the FX horror-drama anthology series American Horror Story with previous collaborator Ryan Murphy. The first season, starring Jessica Lange, Connie Britton and Dylan McDermott, premiered October 5, 2011, and received critical acclaim; the series was nominated for 17 Primetime Emmy Awards in 2012, and 15 Primetime Emmys in 2013, with Falchuk nominated for Outstanding Miniseries or Movie both years. In 2014, the show was once again nominated for 17 Primetime Emmy Awards, with Falchuk nominated for Outstanding Writing for a Miniseries, Movie or a Dramatic Special. Falchuk is an executive producer on American Crime Story with Ryan Murphy, which began airing on Tuesday, February 2, 2016. In October 2014, it was announced that Fox had given a 15 episode straight-to-series order for Scream Queens, a horror-comedy anthology series created by Falchuk, Murphy and Brennan. The first season, set on a college campus, starred Emma Roberts, Lea Michele, Abigail Breslin, Keke Palmer and Jamie Lee Curtis, and premiered in the fall of 2015.