James Rodriguez scored his first goal of the season late in the first period, before Karim Benzema doubled the advantage in the 72nd minute as Real Madrid recorded a club-record 16th straight league win.
Real Madrid were without both Cristiano Ronaldo and Gareth Bale for the contest in Barcelona, with the former missing out through illness and the latter still struggling with the hip problem that he picked up against Sporting Lisbon.
Benzema retained his spot at centre-forward, while it was Lucas Vazquez and Marco Asensio in the wide positions. James and Pepe were also given starting roles as Zinedine Zidane shuffled his pack from the Champions League clash against the Portuguese giants on Wednesday night.
As for Espanyol, head coach Quique Flores made just one change from the team that drew 1-1 with Real Sociedad last time out - Pape Diop replacing the suspended Javi Fuego, who picked up a red card against the Basque side.
Real Madrid had two good opportunities to make the breakthrough inside the opening 10 minutes, but Asensio just failed to connect on a dangerous Vazquez cross, before Ramos headed a James corner wide of the post from inside the box.
Espanyol had a super chance of their own in the 11th minute when a mistake from Pepe presented Leo Baptistao with space inside the Real Madrid box, but the striker could not find a route past Kiko Casilla. Alvaro Vazquez then struck one over the crossbar from distance as the home side threatened once again.
The opening 20 minutes was very stop-start, however, with a series of challenges forcing the referee into action and both Pablo Piatti and Casemiro had to be replaced after picking up injuries for each team.
Real Madrid had the ball in the back of the net five minutes before the break when Benzema headed a Marcelo cross into the bottom corner, only for the linesman to raise his flag. Espanyol then had a chance of their own moments later as Baptistao met a Hernan Perez cross, but the striker's header just dropped wide of the post.
The visitors did make the breakthrough in the second minute of stoppage time at the end of the first period, however, when James rode a couple of challenges outside the Espanyol box before curling a low effort out of the reach of Diego Lopez and into the bottom corner to cap his first start of the season with a goal.
It was a decent start to the second period from Espanyol, with Baptistao causing Ramos and Pepe problems inside the Real Madrid box. The hosts had a shout for a penalty in the 53rd minute when Pepe left Baptistao in a heap, but the referee was not interested and play continued.
Real Madrid had a chance to score a second just before the hour when Benzema spun inside the Espanyol box and produced an overhead kick towards the top corner, but Lopez was on hand to save.
Espanyol were struggling to create opportunities as play developed, however, and a long-range strike from Perez missed the target as the home side's frustrations grew with little over 25 minutes of football to play in Barcelona.
The visitors had another opportunity 20 minutes from time when Benzema sent a curling effort towards the bottom corner, but Lopez was on hand to deny his former teammate once again. Benzema was not to be denied though and scored his first goal of the season in the 71st minute when he fired a low Vazquez cross into the bottom corner of the net.
Espanyol almost hit back through Felipe Caicedo moments later, but his deflected effort was pushed over by Casilla, before Baptistao struck harmlessly wide of the post 10 minutes from time as Espanyol's frustrations continued.
Isco came close to a third for Real Madrid late on, but the Spaniard's curling effort was saved by Lopez, before the goalkeeper kept out a Ramos free kick as it finished 2-0 to the visitors on the night.
Next up for Real Madrid is a home match against Villarreal on Wednesday night, while Espanyol will look to record their first win of the season when they travel to Osasuna one day later.