Ronaldo netted from the penalty spot in the first half and Higuain raced clear to double the lead in the 76th minute, but there was little else of note in a low key game.
Real moved on to 77 points with eight matches left to play, ahead of Barca on goal difference, after the champions swept aside sixth-placed Athletic Bilbao 4-1 on Saturday.
With Real notching up their 12th straight league victory and Barca having only lost once all season, next Saturday's 'Clasico' at the Bernabeu is being seen as crucial to the outcome of the title.
Ronaldo was brought down as he dribbled into the area after 23 minutes at the Sardinero, and the Portuguese forward scored from the ensuing penalty.
Real made sure of the points when Alvaro Arbeloa sent Argentine Higuain through for his 24th league goal, and Guti and Ronaldo both went close to adding to the score in the closing stages.
Earlier, Spain striker David Villa scored twice in the last five minutes to help keep Valencia on course for next season's Champions League with a 3-0 win at home to Osasuna.
Winger Joaquin struck just after the break at Mestalla and Villa scored in the 89th and then again from the penalty spot in time added on.
Third-placed Valencia have 56 points from 30 games, eight ahead of Sevilla in fourth, and moved a step closer to securing Spain's last automatic Champions League qualification place.
Real Mallorca needed a late goal from Pierre Webo to grab a 1-1 draw away to Almeria, that put them level on 48 points with Sevilla, but fifth due to their inferior head-to-head record.
Villarreal are seventh on 43 points after a 2-0 win away to troubled Real Valladolid and Diego Forlan scored in his fifth consecutive game as Atletico Madrid beat eighth-placed Deportivo Coruna 3-0 to go 10th on 40.
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