See main article: 2010 Mutua Madrileña Madrid Open.
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.
The four Rome semifinalists received a bye into the second round. They are as follows:
Serena Williams (third round)
Jelena Janković (quarterfinals) Ana Ivanovic (second round)
María José Martínez Sánchez (second round)