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

Bye 
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)

Draw

Finals

Top half

Section 1

Section 2

Bottom half

Section 3

Section 4

References
Main Draw
Qualifying Draw

Women's Singles