Williams was previously set to face Qiang Wang in the third round of tournament play.
Serena Williams has withdrawn from the Miami Open due to a left knee injury, the tournament announced on Saturday.
"I am disappointed to withdraw from the Miami Open due to a left knee injury,” Williams said in a statement. “It was an amazing experience to play at the Hard Rock Stadium this year and would like to thank the Miami Open for putting on an amazing event."
Williams, 37, was coming off of a tough three-set victory over Rebecca Peterson on Friday, winning 6-3, 1-6, 6-1 to reach the third round. Williams would have faced Qiang Wang in the fourth round on Sunday.
Saturday's withdrawal marks the second consecutive tournament in which Williams has been forced to withdraw. At the Indan Wells Open in early March, Williams claimed a 7-5, 6-3 victory over two-time Grand Slam winner Victoria Azarenka before retiring from her third-round match against Garbine Muguruza due to a viral illness.
"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," Williams said.
Wang will automatically advance to the fourth round.