Powell was born in West Philadelphia and later moved to California. Powell graduated from St. Mark's High School in Wilmington, Delaware and earned his Bachelor of Fine Arts degree at New York University's Tisch School of the Arts in 2001.
In the spring of 2007, while working as a recurring character on 30 Rock, he shot an ABC pilot called Judy's Got A Gun. It was not picked up for the Fall 2007 season, and Powell returned to 30 Rock, where he was promoted to a series regular. In October 2008, Powell launched and starred in a self-funded web series called Keith Powell Directs a Play chronicling Powell’s foray into directing Uncle Vanya at a fictional repertory theatre group. In 2009, Powell was a guest commentator on VH1's 100 Greatest One Hit Wonders of the 80s, and also played a Tuskegee Airman in the movie Night at the Museum: Battle of the Smithsonian.
In 2014, Powell began a recurring role on the television series About a Boy as Richard, Will's workaholic friend/accountant/business manager.
Powell recurred on the final season of The Newsroom. He appeared in the feature film My Name Is David. In 2015, he created, wrote, directed, and starred in the web series Keith Broke His Leg. The series went on to win several Indie Series Awards, including Best Comedy Series and Best Actor in a Comedy.
Powell began his television directing career in March 2018 with the season 3 episode "Amnesty" of the NBC television series Superstore. The episode was critically well received, specifically for juggling the various love story plot points of the major characters.
