The fifth-seeded Williams was two points from victory several times in the second set, including leading 5-1 in the tiebreaker. But Razzano won six straight points to force a third set, and then took control.
Williams entered the day with a 46-0 record in first-round matches at Grand Slam tournaments. She had been looking for her 14th major title, and second at Roland Garros.
Razzano won on her eighth match point.
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