Simeone named Joao Felix, Koke and Marcos Llorente among the substitutes with key games against Salzburg and Real Madrid to come over the next week, and Atleti struggled to get going as a result.
Llorente was introduced at half-time and Joao Felix and Koke followed before the hour, though Lemar had made the all-important breakthrough a few moments earlier with his first club goal since April 2019.
Atleti were in control from that point and added a second through substitute Llorente's route-one strike as the leaders made it seven league wins in a row to move above Real Sociedad.