Williams suffers from persistent knee problems.
"I was really hoping my knee would heal in time to play the Family Circle Cup, as it's one of my favorite stops on the tour," Williams said in a statement released by tournament officials. "Unfortunately my knee has not fully healed in time and I am now looking forward to returning to the WTA Tour in Europe."
Williams withdrew from the tournament last year with a left leg injury.
Defending champion Sabine Lisicki also pulled out of the tournament with a left ankle injury. She defeated Caroline Wozniacki in last year's final.
Notable deaths of 2014 [PHOTOS]