Jose Mourinho's side were not wholly convincing but a Mesut Ozil double and Karim Benzema ensured they went into their Champions League semi-final on the back of a win
The visitors gave a good account of themselves in the capital, but Mesut Ozil managed to break the deadlock on the stroke of half time. Karim Benzema added a second soon after the restart and the German completed a late double, ensuring victory ahead of their Champions League semi-final with Dortmund, despite Jorge Molina having scored from the spot beforehand.
Following an open start to the game, Betis thought they had taken a surprise early lead when Ruben Castro lashed the ball into the roof of the net. The striker pounced as Diego Lopez failed to get Nosa Igiebor's header to safety only to see the referee's assistant raise his flag for an offside decision.
Madrid refused to rush into asserting themselves on the game and continued the game at a calm tempo.
Marcelo was forced from the field of play in the 13th minute due to injury, and his energy was missed down the left. Ronaldo and Jose Callejon both missed the target as the final touch remained elusive for the hosts.
Despite their defensive deficiencies, at the other end the Seville outfit impressed with crisp passing and fluid movement among the forwards. Joel Campbell sent an acrobatic volley just wide after a speedy Dorlan Pabon run and cross before Castro sent a header just over the bar in the 37th minute.
Ronaldo sent a warning in the 39th minute as his thunderous 25-yard shot cannoned back off the post, but Pabon responded in kind by rattling the bar with a sterling effort soon after.
However, los Verdiblancos could not hold out until half time and in the 45th minute Ozil found the net. Moving in field from the right following a give-and-go with Benzema, the German shaped to shoot for the far corner but guided the ball past Adrian at his near post.
Los Blancos improved after the break and they doubled their advantage 12 minutes into the second half. Ronaldo rolled a pass into the area which Benzema latched onto and squeezed a shot past Adrian and inside the near post.
But Betis did not shy away and after Pabon had seen a couple of ambitious attempts fail to stretch Diego Lopez, they were awarded a penalty in the 73rd minute. Nacho brought down Castro in the area and Molina scored from the spot despite the keeper getting a hand to it.
Pepe Mel's team pressed for an equaliser but Castro was denied by the frame of the goal after pouncing on Ricardo Carvalho's short header back to Lopez, and Raul Albiol blocked Pabon's follow-up on the line.
Ozil wrapped up the win, temporarily moving Barcelona to within 10 points of Barcelona, when he diverted Callejon's volley into the back of the net in stoppage time.
Betis, meanwhile, could find themselves nine points adrift of Champions League qualification should results go against them.