There were changes, with Gareth Bale, Marcelo and Dani Carvajal all rested, the latter not even included on the bench, following Real's win over Roma in the Champions League on Wednesday
Real Madrid moved top of La Liga on Saturday after Marco Asensio's goal proved the difference in a scrappy 1-0 win over Espanyol.
Their victory at the Santiago Bernabeu may only give Madrid 24 hours above Barcelona, who play Girona on Sunday, with their perfect record still intact.
More pressing for Julen Lopetegui will be the defensive slackness that made this arguably the least assured of the six competitive games he has overseen so far, including last weekend's draw away to Athletic Bilbao.
Real Madrid take the lead thanks to Asensio pic.twitter.com/i6TztYgF8d— Goal (@goal) September 22, 2018
There were changes, with Gareth Bale, Marcelo and Dani Carvajal all rested, the latter not even included on the bench, following Real's win over Roma in the Champions League on Wednesday.
But if they gift Atletico Madrid the same chances in the city derby next weekend, they may not find their opponents so generous. Atletico had earlier ground out a 2-0 win away to Getafe.
"The game was nervous and in the last 15 minutes we lacked control," Lopetegui said. "These post-Champions League games are always really dangerous and we know it."
Carvajal's absence meant a debut for Alvaro Odriozola, who joined from Real Sociedad in the summer, while Thibaut Courtois replaced Keylor Navas to continue Lopetegui's rotation strategy in goal.
Espanyol twice could have scored on the counter-attack. The first sprung from a poor header from Raphael Varane but Pablo Piatti dragged his finish wide.
Soon after they were in again, as Hernan Perez's shot had to be parried by Courtois and Didac Vila's rebound blocked by Casemiro.
The hosts were more impressive going forward and in the 41st minute, they took the lead. Luka Modric's scuffed shot landed kindly at the feet of Asensio and he did brilliantly to harpoon the ball into the far corner.
Referee Mateu Lahoz ruled the goal out for offside but Real were saved by VAR and then later the crossbar, as Borja Iglesias' scooped finish was denied late on.
"We are not going to win 5-0 every game," Varane said.
Atletico's victory was more comfortable and they had Thomas Lemar to thank after the Frenchman scored his first goal for the club and instigated another against Getafe.
The result was all but secure when Getafe's Ivan Alejo was sent off shortly after the hour for a dangerous tackle on Saul Niguez.
Real Madrid get the job done 💪 pic.twitter.com/T3onMSJIp4— B/R Football (@brfootball) September 22, 2018
Atleti had not lost to Getafe, or even conceded a single goal, in 13 previous meetings but victory meant more to Diego Simeone's side after just one win from their opening four league games.
This was also the first time Lemar looked like the player Atletico must have hoped they bought when they spent 72m euros ($84 m) on him in the summer.
"It's something big, I will never forget it," Lemar said. "The coach trusts me and it's the least I can do to repay his faith."
The first goal was almost a cracker as Lemar collected the ball off Antoine Griezmann 30 yards out and let rip with his left foot. Soria was beaten but the crossbar was not, and it needed an unfortunate deflection of the goalkeeper to find the net.
GOOAAALLLL! Real lead https://t.co/pPOGByROus— Mirror Football (@MirrorFootball) September 22, 2018
There was no doubt about the second after half-time. A sweeping move saw Atletico move the ball from right to left, with Koke applying the final pass in behind. Lemar touched it around Soria and made no mistake.