Julián Alvarez levelled for Atlético after Rodrygo Goes sent the hosts ahead, but Brahim Díaz stroked home the winner for the record 15-time winners to delight the Santiago Bernabeu stadium.
Diego Simeone’s Atlético, who lost in the 2014 and 2016 finals against their bitter rivals, kept stars Vinicius Junior and Kylian Mbappé quiet but still came up short.
The Rojiblancos played it safe in the final stages, seeming to accept their one-goal disadvantage for the second leg derby clash at home next week.
Madrid coach Carlo Ancelotti opted for Morocco international Díaz in midfield to replace the suspended Jude Bellingham and selected Fede Valverde at right-back after he was passed fit to play.
The Italian had demanded his side show a better attitude and more commitment than during their La Liga defeat by Real Betis on Saturday and his charges delivered.
Rodrygo pounced after just four minutes, slipping inside Javi Galán to collect Valverde’s teasing pass before firing home with his left foot across Jan Oblak and inside the far post.
“For a moment we had the game under control, but we knew that it would not be an easy match, because they were at home and they have great players,” Alvarez said.
“But we know there are 90 minutes to go,” he added. “It’s one goal, and another game, at home with our fans.”
It was the Brazilian winger’s fifth strike of the tournament, habitually shining on the European stage for Madrid, where he boasts 25 goals in 61 appearances.
Rodrygo wanted a penalty when Galán appeared to hold him back in the area but his appeals were waved away.
Atlético host Real Madrid next week at the Metropolitano stadium, with the winner facing Arsenal or PSV Eindhoven in the quarter-finals.
Arsenal all but ensured a quarter-final berth as they crushed a shambolic PSV 7-1 in Eindhoven.
Jurrien Timber headed Arsenal into the lead on 18 minutes before Ethan Nwaneri smashed a second. Mikel Merino, from a narrow angle, put the visitors three goals up in just the 31st minute.
Noa Lang hit back with a PSV penalty before half-time. But Martin Odegaard slotted home a rebound and Leandro Trossard dinked a goal as Arsenal scored twice in the first three minutes of the second half.
Odegaard added another with 12 minutes left and then set up defender Riccardo Calafiori, a first-half replacement, to round off the scoring.
“We were fluid. We had enthusiasm, the drive and the hunger,” Arsenal midfielder Declan Rice said. “We need to keep pushing as a team with the mentality.” (AFP)
