Mattek-Sands, in one of the day's early matches, eliminated Li 5-7, 6-3, 6-2. She won seven consecutive games in one stretch in building a 5-0 lead in the third set, and has reached the third round of a major tournament for a third time.
She played in the French Open third round in 2011 -- the year Li won the event -- and made the fourth round of the 2008 Wimbledon Championships.
Mattek-Sands managed seven breaks on the day, with three in the third set.
Rain was again an issue in Paris, with play suspended several times. Tournament officials called off play for the day about 9 p.m., with defending champion and second-seeded Maria Sharapova on the court. She was leading Eugenie Bouchard 6-2, 4-2 with Bouchard serving ad-in when play was stopped.
Third-seeded Victoria Azarenka was able to play a match delayed by rain Wednesday, beating Annika Beck 6-4, 6-3. Azarenka had six double faults and 26 unforced errors, and won 55 percent of the points off Beck's serve and had six breaks.
Martina Erakovic ousted 16th-seeded Dominika Cibulkova 6-2, 2-6, 6-4.
Also advancing were Zheng Jie, Paula Ormaechea and Jamie Hampton.