The American broke her title drought in the tournament with a win over Maria Sharapova, 6-4, 6-4.
The defending champion out of Russia will have hands full against Williams, who has won all but two matches this year.
Rafael Nadal beat Novak Djokovic in five sets to progress into the French Open final.
Rafael Nadal and Novak Djokovic meet in the semifinals of the French Open at Roland Garros.
The Spaniard defeated Stanislas Wawrinka at the French Open, 6-2 6-3 6-1.
Maria Sharapova defeated Jelena Jankovic despite failing to win a game in the first set.
Two of tennis's biggest stars take center court at Roland Garros, and can force a rematch from their battle in Monte Carlo earlier this year.
Jo-Wilfried Tsonga defeated Roger Federer in straight sets on Tuesday.
Rafael Nadal breezed past Kei Nishikori in the fourth round of the French Open.
Perhaps the two best players in the world at this moment, the Serb and Spaniard appear to be on a collision course.
The No. 1 player in the world trounced Caroline Garcia in an impressive third-round victory at Roland Garros.
Novak Djokovic played three hard-fought sets in his win over David Goffin.
The King of Clay had trouble with Germany's Daniel Brands in a four-set win.
No. 1 Novak Djokovic could face the Spaniard as early as the quarterfinals in the 2013 French Open
Djokovic claims that the French Open is his top priority in 2013.
Tennis star Maria Sharapova confirmed her relationship with fellow professional athlete, 22-year-old Grigor Dimitrov.