| Champ: | Roger Federer |
| Runner: |  Tomáš Berdych |
| Score: | 3–6, 7–5, 7–5 |
See main article: 2012 Mutua Madrid Open.
Roger Federer defeated Tomáš Berdych in the final, 3–6, 7–5, 7–5 to win the men's singles tennis title at the 2012 Madrid Open. With the win, Federer won his record-tying 20th Masters title and third title at Madrid.
Novak Djokovic was the defending champion, but lost to Janko Tipsarević in the quarterfinals.
This was the first and only edition of the tournament to be held on blue clay courts.
The top eight seeds receive a bye into the second round.