At the Porsche Tennis Grand Prix, Šafářová upset world No. 2 and top-seed, Caroline Wozniacki, in the second round. She then fell in three sets to qualifier Anna Lapushchenkova in the quarterfinals. At the Italian Open, she upset world No. 9, Agnieszka Radwańska, in the third round, but lost to eventual champion Martínez Sánchez, in straight sets in the quarterfinals. At the Madrid Open, she upset world No. 12 Maria Sharapova in the first round. She then defeated Olga Govortsova and Alexandra Dulgheru to advance to the quarterfinals, where she beat world No. 18 Nadia Petrova. She retired due to a thigh injury while trailing Aravane Rezaï by a set in the semifinals. At the French Open, she was seeded 24th. She defeated Jelena Dokić in the first round, but was defeated by Polona Hercog in the second round. The French Open would be her best singles result at a Grand Slam in 2010 as she lost in the first round at both Wimbledon and the US Open.
