The seven-times grand slam singles champion was ranked 139th in the world at the entry deadline for the U.S. Open, while the cut-off for automatic main draw entries was 102.
The 24-year-old Williams, now up to 79th, won the tournament in 1999 and 2002.
Joining Williams as wildcard entries into the singles draw are former top 10
The two-week U.S. Open begins on Aug. 28.