Messi's 40th goal of the season in all competitions put the reigning Spanish and European champions on the road to a 2-0 victory in 'El Clasico', with Pedro Rodriguez completing the scoring 10 minutes after half-time.
The result ended Madrid's 12-match winning streak in La Liga and their 100% record at the Bernabeu, which had stood at 15 successive triumphs, but more importantly it put Barca in pole position to retain their league crown.
Not only are they three points clear of Madrid with seven games to go, but they also boast the better head-to-head record if the two clubs should finish level.
Messi declared at the final whistle: "Will this win us the league? There are still games left to go. We have some tough away matches, but yes, we took a big and important step tonight.
"It was a close game because both teams respect each other a lot - we both know each other well so there's a lot of respect. But when we had chances we took them, and that's why we won."