After nine years as a regular on the British Channel 4 hit improvisation series Whose Line Is It Anyway?, Colin Mochrie became a regular on the American version hosted by Drew Carey which aired on ABC. On there, his baldness became something of a running gag. At the same time, he starred in the Canadian comedy series Blackfly and Supertown Challenge.

Mochrie was a guest star of The Drew Carey Show for three episodes: She's Gotta Have It, Drew Live, and Drew Live II.

Mochrie currently stars on the CBC show Getting Along Famously, and on The WB Television Network series Drew Carey's Green Screen Show.

In March 2005, a Nabisco advertising campaign starred Mochrie as the "Snack Fairy", in which he wears a tutu.

Mochrie was a guest on the series Distinguished Artists. Today, teamed up with Brad Sherwood, he tours the United States and Canada performing classic improv games from "Whose Line." He also sometimes is found touring with other Whose Line alumni in the Improv Allstar shows. Mochrie has also made two small guest appearances on The Red Green Show as "Frank Kepke," an expert on all kinds of hot dogs and weiners, and he sometimes makes regular objects out of them.

He, along with Rosie O'Donnell, also hosts a video introduction to a tour of the bakery in the Pacific Wharf area of Disney's California Adventure. He also helps explain, in the video, how sourdough bread is made.