Isner then played at the 2010 French Open; his ranking assured his first direct seed into a Grand Slam event. Seeded 17th, he defeated Andrey Golubev in the first round for his first singles victory at the French Open. He advanced to the third round, before losing to the no. 15 seed and eventual semifinalist Tomáš Berdych. In doubles, he and Querrey were the 12th seeds, but withdrew prior to the start of the tournament after Querrey's first-round loss in singles.