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 was in control from that point and added a second through substitute Llorente's route-one strike as the leader made it seven league wins in a row to move above Real Sociedad, which travels to Alaves on Monday (AEDT).
Jordi Masip spilled Angel Correa's long-range shot but Luis Suarez could not take advantage four minutes into his return, miscontrolling the ball as he attempted to round the keeper.
The visitors entered the game unbeaten in three and looked the more threatening in the first half, with Jan Oblak keeping out efforts from Oscar Plano and Marcos de Sousa.
Simeone's men were given another scare four minutes into the second period when De Sousa's volleyed shot at the back post was blocked by Kieran Trippier in front of goal.
But Atletico grew into the game and, a few moments after Correa fired wide on the turn, Lemar converted Trippier's cross from a tight angle after Suarez failed to reach it at full stretch.
That ended a run of 45 games in all competitions without a goal for the France international and Atleti had a second 16 minutes later, Trippier flicking on Oblak's pass for Llorente to race through and tuck past Masip.