Gilbert, of the Omega Pharma Lotto team, is the reigning Belgian champion. In the hilly race, he shot away from a small breakaway group with only 4 kilometres to go.
Samuel Sanchez tried to catch the Belgian, but he didn't succeed. Gilbert had the time to celebrate in the last 500 metres and took his time to straighten his shirt and throw his hands in the air .
2009 winner Carlos Barredo of Spain came second, 12 seconds behind Gilbert, with Greg Van Avermaet taking third place in the sprint. Dries Devenyns finished fifth and Jelle Vanendert 10th.
Earlier this season, Gilbert had already picked up classical victories in the Amstel Gold Race, Flèche Wallonne and Liège-Bastogne-Liège.
It had been 28 years since a Belgian last won the Clásica, with Claude Criquiélion in 1983.