Vinícius Júnior scored for Madrid, which had already sealed second place.
Mbappé started for Real Madrid three days after saying coach Álvaro Arbeloa had made him the team's fourth-choice striker. He came off the bench in the win at Oviedo on Thursday in what was his return from an injury layoff.
Sevilla avoided relegation despite a 1-0 loss to Real Madrid at home. It was a tight relegation fight coming into Sunday's matches and Sevilla secured its salvation thanks to other results.
Relegation battle update
Alaves also guaranteed top-tier soccer next season with a 1-0 win at already relegated Oviedo.
Levante moved closer to safety with a 2-0 win over Mallorca and is 15th with 42 points, the same number of points as 16th-place Osasuna and 17th-place Elche.
Osasuna lost 2-1 to Espanyol at home, while Elche beat 10-man Getafe 1-0.
Inside the relegation zone are 17th-place Girona (40 points), second-to-last Mallorca (39) and Oviedo (29).
Five teams will enter next weekend's final round looking to avoid the drop: Levante, Osasuna, Elche, Girona and Mallorca.