Pique then took advantage of some poor marking to put Barca back ahead, controlling with his chest before scoring with a volley.
Atletico tried to pressure Barcelona high up the park, but the visitors were controlling the ball and Villa was inches away from setting Messi up for a second goal before the break.
Xavi Hernandez went close with a shot from distance after half time, but De Gea produced a flying save.
The game was becoming bogged down in midfield and Atletico coach Quique Sanchez Flores opted to replace Garcia with Thiago, but Barcelona continued to create the best chances with Villa a constant threat, although Messi missed a guilt edged chance to seal the points five minutes from time.
Atletico defender Ujfalusi was sent off for a foul on the Argentinean deep into injury time. Messi was carried off on a stretcher, but by then the game was won.
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