Aravane Rezaï defeated Venus Williams in the final, 6–2, 7–5 to win the women's singles tennis title at the 2010 Madrid Open. Dinara Safina was the defending champion, but lost to Klára Zakopalová in the first round.

Seeds

• # 🇺🇸 Serena Williams (third round) • # Caroline Wozniacki (second round) • # 🇷🇺 Dinara Safina (first round) • # 🇺🇸 Venus Williams (final) • # 🇷🇺 Svetlana Kuznetsova (first round) • # 🇷🇺 Elena Dementieva (second round) • # 🇷🇸 Jelena Janković (quarterfinals) • # 🇦🇺 Samantha Stosur (quarterfinals) • # 🇵🇱 Agnieszka Radwańska (second round) • # 🇧🇾 Victoria Azarenka (first round, retired due to right adductor strain) • # 🇷🇺 Maria Sharapova (first round) • # 🇫🇷 Marion Bartoli (second round) • # 🇨🇳 Li Na (quarterfinals) • # 🇮🇹 Flavia Pennetta (second round) • # 🇮🇹 Francesca Schiavone (third round) • # 🇷🇺 Nadia Petrova (quarterfinals)

Bye

The four Rome semifinalists received a bye into the second round. They are as follows:

Draw

Finals

Top half

Section 1

Section 2

Bottom half

Section 3

Section 4