The world No. 1 announced in a statement on Friday that she originally hurt her leg at the Sony Ericsson Open in Miami, where she lost to Victoria Azarenka in the final last weekend.
Azarenka withdrew from the Family Circle Cup on Tuesday because of an injured right shoulder.
Williams' sister Venus and No. 3-ranked Elena Dementieva are among those slated to play in the tournament starting on Monday.
Serena Williams withdraws from Family Circle Cup