A native of Kent, Washington, Mayne was an honorable mention junior college All-American quarterback at Wenatchee Valley Community College Wenatchee, WA in 1978. Kenny Mayne graduated from UNLV in 1982, with a degree in Broadcasting, where he was the back-up quarterback and ahead of future NFL star Randall Cunningham on the depth chart. While at UNLV, Mayne played football for two years and later signed as a free agent with the Seattle Seahawks.

Kenny started at ESPN in 1994 as a SportSmash anchor on ESPN2, and soon moved over to the main network. He became well known for his dry sense of humor and his unique home run calls, such as "Yahtzee!", "I am amused by the simplicity of this game!" and "I am king of the diamond! Let there be an abundant clubhouse feast! Bring me the finest meats and cheeses in all the land!", and "the ball was hit over some fencing that they've constructed in the outfield.". He would also routinely thank the viewers for having electricity.

For a time, he served as co-anchor of the 11PM SportsCenter with Dan Patrick, and also hosted the game show 2 Minute Drill. Kenny is now most often seen as commentator for select horse racing events, as well as providing offbeat feature stories on Sunday NFL Countdown in a weekly segment called "The Mayne Event."

ESPN hired Mayne in 1994 after Mayne had sent ESPN a note inquiring whether or not the network would hire him. The note simply asked to check a box, including one option which read, "We'll hire you when there's an ESPN5."

In January 2006, Mayne participated in the second season of ABC's Dancing with the Stars, but after a disastrous Cha Cha, Mayne was the first contestant to be eliminated in the first round.