Williams was stunned in the first round of the 2012 French Open by Virginie Razzano but she has been on a tear since then, winning 10 tournaments. Those titles include Wimbledon, the Olympics and the U.S. Open last year and five this year.
Williams is 36-2 this year and has won her last 24 matches, a career high.
Even with No. 2-ranked and defending French Open champion Maria Sharapova playing well, Williams is a prohibitive favorite to win her second French Open title. She won her first in 2002.
Williams opens her tournament against Anna Tatishvili but down the draw could face eighth-seeded Angelique Kerber in the quarterfinals. The highest seeds in other quarter of the draw are fourth-seeded Agnieszka Radwanska and No. 5 Sara Errani, last year's runner-up.
There could be an all-Williams semifinal because Venus Williams is in the same half of the draw, but not the same quarter, as Serena.
Sharapova is a healthy 30-4 this year with two titles (three of the losses are to Serena Williams) and is seeking to be the first back-to-back French Open winner since Justine Henin was a three-time winner over 2005-07.
Victoria Azarenka, seeded third, is in the Sharapova half of the draw. She's won two Grand Slam titles (Australian Open 2012-13) but never advanced past the quarterfinals in Paris. Azarenka's potential quarterfinal opponent is 2011 champion Li Na, who is seeded sixth. Sharapova's is seventh-seeded Petra Kvitova.
The French Open begins Sunday and has the women's singles final scheduled for June 8.