Skai Jackson was born in New York City. She began her career as a child model appearing in numerous national commercials, including for Band-Aid bandages.
Her first major acting role was in the independent film Liberty Kid (2007). Followed by other films such as Rescue Me (2008) and The Rebound (2009). In 2009, she was cast member of the Nickelodeon pre-school animated series Bubble Guppies playing role of Little Fish. From 2010 to 2011 she guest starred in the television series Team Umizoomi, Royal Pains and Boardwalk Empire. She also had small role roles in the 2011 films Arthur and The Smurfs.
In 2011, she was cast as Zuri Ross in the Disney Channel sitcom Jessie starring Debby Ryan.