Ronaldo took his league tally for the season to 33, two ahead of Lionel Messi, and gave second-placed Real 83 points with three matches left.
A double from Roberto Soldado helped Valencia to a 3-0 home win over Real Sociedad that gave them 66 points in third place, which offers qualification for next season's Champions League.
Soldado slotted home from close range after a low cross from Juan Mata in the 16th minute and, after Jonas had doubled the lead in the 25th, the striker powered in a header for his 16th goal of the campaign before the break.
At the bottom, a 2-0 defeat for Almeria at Getafe meant they were relegated while second from bottom Hercules are close to joining them after a 3-2 defeat by Racing Santander.
Showing little sign of a hangover from their midweek Champions League semi-final exit at Barca's hands, Real went ahead at the Sanchez Pizjuan when Sergio Ramos headed in from a corner after 21 minutes.
Ronaldo scored after a knockdown from Pepe as Sevilla failed to clear another corner and Kaka finished off a sweeping move just before half-time with a curling shot inside the far post.
Although Alvaro Negredo pulled one back for the hosts just after the hour, Ronaldo rattled in three goals in 10 minutes and could have had more before Negredo headed a late consolation for Sevilla.
ATTACKING VERVE
The attacking verve that was so glaringly absent from their recent 'four-match' series against Barca was too much for Sevilla who slumped to their fourth defeat to Real this season in La Liga and the King's Cup.
Athletic Bilbao survived a late comeback from Levante to secure a 3-2 home win that kept them in pole position for the first of the three Europa League places, with 54 points in fifth spot.
Gaizka Toquero, David Lopez (penalty) and Fernando Llorente put the Basque side 3-0 up early in the second half before the visitors netted twice in the last 12 minutes.
Sevilla are sixth with 52 points ahead of seventh-placed Atletico Madrid on the head-to-head rule after the Europa League holders suffered a 3-0 home defeat against surging Malaga.
Manuel Pellegrini's Malaga were inspired to their fourth win on the trot by Julio Baptista, who scored one goal and set up another, and along with fellow strugglers Getafe and Racing boosted their chances of avoiding the drop.
Racing climbed to 11th with 43 points, Malaga are 12th with 42, the same as Mallorca in 13th. Sociedad slipped to 14th with 41 and Getafe moved out of the bottom three to 15th with 40 points.
Almeria's fate was out of their hands when they kicked off against Getafe and goals early in each half from Adrian Colunga and Pedro Rios sealed relegation.
