Zinedine Zidane's men led the league by virtue of their superior head-to-head record going into the weekend and were boosted by Celta's late equaliser against Barca.
Madrid made sure not to pass up the opportunity to build a gap at the summit as Casemiro scored following a wonderful Karim Benzema assist in an entertaining if ultimately narrow away victory.
The capital club has control of the title race with just six matches remaining, although it was not all one-way traffic at RCDE Stadium despite bottom side Espanyol's accommodating defending.
Madrid looked similarly shaky at times in the first half as Sergi Darder saw an early deflected shot trickle wide before Wu Lei wastefully blasted over.
Former Madrid goalkeeper Diego Lopez scrambled to keep out an ambitious Casemiro attempt and watched both Sergio Ramos and the Brazil international head over, the captain missing the target from point-blank range.
Benzema was next to try his luck and draw a save from Lopez, whose busy outing continued with a double stop from Casemiro and Eden Hazard in a goalmouth scramble prompted by his own failure to deal with a high cross.
Casemiro's fifth effort before half-time finally evaded Lopez to break the deadlock, though, as Benzema teed up his team-mate with a cute backheel through Bernardo Espinosa's legs.
Madrid's momentum was slowed by the break, yet subsequent speculative Espanyol efforts from distance did not cause Thibaut Courtois significant concern as another win was sealed.