"I am disappointed to withdraw from the Miami Open due to a left knee injury," the former world number one said in a statement.
"I hope to be back next year to play at this one-of-a-kind tournament in front of the incredible fans here in Miami."
The eight-times Miami champion had begun the tournament with a tough three-set victory over Sweden's Rebecca Peterson, winning 6-3 1-6 6-1 on Friday.
"I knew I could play a lot better than I was playing," Williams had said afterwards of her error-ridden second set.
"I just said, 'Okay, you're better than this, Serena.'"
At Indian Wells, Williams had claimed a 7-5, 6-3 victory over two-time Grand Slam winner Victoria Azarenka before being forced to retire from her third round match against Garbine Muguruza, when trailing 6-3, 1-0.
(Reporting by Gene Cherry in Raleigh, North Carolina; Editing by Ian Chadband)
