Karim Benzema headed in a whipped cross from James Rodriguez after seven minutes and then Ronaldo won and struck home a penalty.
A Rodriguez strike was deflected in after 16 minutes and Ronaldo showed a sublime touch to beat two players and curl a 20 yard shot into the corner before halftime.
Ronaldo headed in from close range after 82 minutes and is now joint top scorer in La Liga on 19 goals with Barcelona's Luis Suarez.
Espanyol's misery was complete with an own-goal from Oscar Duarte.
Barca are three points clear, on 51 points, after their 2-1 victory in the top of the table clash with Atletico Madrid on Saturday.
Ronaldo gave his backing to coach Zinedine Zidane with the side having scored 16 goals in three home games since he took over from Rafa Benitez.
"Zidane is doing well and you can see the results on the pitch," Ronaldo told reporters.
"Zidane has come with a different idea of work and the atmosphere is better. We are winning by big margins.
"We will keeping chasing Barcelona and Atletico, and see where we are at the end of the season."
Valencia manager Gary Neville's wait for a first La Liga win continued after a 1-0 home defeat by lowly Sporting Gijon.
Former England and Manchester United defender Neville, who took on his first head coaching job at the start of December, has gone eight league games without a victory.
Valencia have slipped to 12th place and have not won in 11 La Liga games in total, including under previous coach Nuno Espirito Santo, their worst run since 1986.
Antonio Sanabria's 50th-minute penalty gave Sporting victory.
Kevin Gameiro, Vicente Iborra and Yevhen Konoplyanka were on target for in-form Sevilla who moved up to fifth with a 3-1 victory over Levante.
(Reporting by Tim Hanlon in Barcelona, editing by Justin Palmer)
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