It was a much-needed return to winning ways for Jose Mourinho's side after the shock of Wednesday's Champions League semi-final elimination by Bayern Munich and they could clinch the title later on Sunday if second-placed Barcelona lose at Rayo Vallecano (1930 GMT).
Karim Benzema contributed a quickfire double early in the second half as Real moved on to 91 points with three games left, with Barca, whose three-year stranglehold on the Spanish title is almost certainly drawing to an end, 10 adrift on 81.
The holders were also dumped out of Europe in midweek, losing 3-2 on aggregate to Chelsea on Tuesday, and were stunned three days later by the news that coach Pep Guardiola was stepping down after four years during which he led the team to 13 trophies.
"We won this game which was very important and now we'll carry on so we can close out the league title," Benzema said in an interview with Spanish television.
"The Champions League is finished so now we need to make sure we win the next most important competition," added the France international.
Ronaldo's 19th-minute opener at the Bernabeu, scene of Real's dramatic penalty shootout defeat to Bayern, was his 57th in all competitions and he became the first player since Everton's Dixie Dean 80 years ago to score 43 league goals in a season.
Benzema made it 3-0 with goals in the 48th and 52nd minutes as Sevilla, who squandered a host of good chances, were swatted aside. The Andalusians are ninth on 46 points and in danger of missing out on a lucrative place in Europe next season.
Benzema's brace took his league tally for the campaign to 20 and with strike partner Gonzalo Higuain on 21 it is the first time three players from one club have scored 20 or more goals in a La Liga season. Their combined total of 84 is 30 more than third-placed Valencia.
Valencia can strengthen their grip on an automatic place in next season's Champions League with a win at fifth-placed Malaga later on Sunday (1600 GMT).
Unai Emery's side have 55 points while ambitious, Qatar-owned Malaga are tied on 52 with fourth-placed Levante, who won 3-1 at home to Granada on Saturday.
Athletic Bilbao and Atletico Madrid both have 48 points in sixth and seventh respectively, ahead of their games at Real Zaragoza (1400) and Real Betis (1745).
The Europa League finalists, who face off in the competition's showpiece in Bucharest on May 9, are level on points with eighth-placed Osasuna, who drew 1-1 at Villarreal on Saturday.