Cho, who is of Korean American descent, was raised in Knoxville and went into stand-up comedy in 1986.
He attended University of Tennessee at Knoxville, and moved to Los Angeles, California in 1989 to pursue his career, but always with the intent of returning to his roots in Tennessee.
Cho often uses his childhood experiences as an Asian American in the South in his comedy. "I'm an Asian with a Southern accent," remarks Cho, "To a lot of people, that right there is funny." He frequently makes remarks about the church he goes to, however, not in a mocking way.
Cho appeared on many television shows in late-1980s and early-1990s including Bob Hope's Young Comedians Special, MTV's 1/2 Hour Comedy Hour and VH-1's Stand-Up Spotlight.
He has appeared in three feature films. First, starring opposite Tom Arnold and David Alan Grier in McHale's Navy. In 2001, he appeared in the Farrelly Brothers' movie Say It Isn't So with Heather Graham and Chris Klein. Most recently, in 2006, he appeared in Material Girls starring Hilary and Haylie Duff.
In 2006, he had his own Comedy Central special entitled Henry Cho: What's That Clickin' Noise?.
In 2007, it was announced that he signed a deal with Touchstone Pictures and American Broadcasting Company to write, produce, and star in a television situational comedy series centered around Korean Americans living in the South.
What's That Clickin' Noise