Razzano, No. 111 in the world, defeated Williams 4-6, 7-6 (7-5), 6-3. It was the first time in 47 Grand Slam events Williams lost in the first round. It also ended her 17-match winning streak on clay courts.
Razzano ended with four breaks, including a pair to build a 5-0 lead in the third set. Williams fought back to 3-5 and had five break-point chances in the final game. But Razzano survived the marathon 30-point final game when Williams' backhand went wide.
Williams, who led 5-1 in the second-set tiebreaker, had 47 unforced errors and won just 43 percent of the points on serve.
Second-seeded Maria Sharapova, seen as one of the top threats to the pre-tournament favorite Williams, needed just 48 minutes to dispatch Alexandra Cadantu 6-0, 6-0. Sharapova dropped just 18 points in the match.
No. 4-seeded Petra Kvitova was a 6-1, 6-2 winner over Ashleigh Barty with 57 winners against 15 unforced errors. Ninth-seeded Caroline Wozniacki was even sharper -- 61 winners versus seven unforced errors -- a 6-0, 6-1 romp over Eleni Daniilidou.
Unseeded players moving into the second round included Urszula Radwanska, Irina-Camelia Begu, Lourdes Dominguez-Lino, Arantxa Rus, Jarmila Gajdosova, Ayumi Morita, Heather Watson, Melinda Czink, Tsvetana Pironkova and Klara Zakopalova.