Morril is one of the fastest-rising stand-up comics in New York City and one of the best joke writers in the scene today. He is a regular on Comedy Central's This Week at the Comedy Cellar, where he appears frequently when not touring cities across the nation. He was named one of Comedy Central's Comics to Watch in 2011 and has performed multiple stand-up sets on The Late Show with Stephen Colbert, The Late, Late Show with James Corden and Conan. He's also had stints on Last Comic Standing, America's Got Talent, @midnight with Chris Hardwick, and Inside Amy Schumer.

Most recently, Sam self-released his stand-up special, Up On The Roof, in which he navigates performing live during COVID. In February 2020, Morril released his 3rd stand-up special for Comedy Central, I Got This on their YouTube channel and received over 1.5 million views within the first two weeks. Morril then later released it as a comedy album with 800 Pound Gorilla Records.

In 2015, the comedian recorded his debut album, Class Act, with Comedy Central Records, which went to #1 on iTunes and made numerous top 10 lists and appeared on season four of Comedy Central's The Half Hour. His first one hour special, Amy Schumer Presents Sam Morril: Positive Influence premiered on Comedy Central in 2018.

Morril was the host of his very own show on MSG called People Talking Sports, which ran for two seasons and received an Emmy® nomination. Morril also has a cameo in the Academy Award nominated film, Joker.