Angel Correa's deflected first-half strike and a Yannick Carrasco goal 10 minutes from time at the Wanda Metropolitano on Friday (AEST) sent Atleti three points clear of Real Madrid at the summit.
Atleti thrashed Eibar 5-0 last weekend after picking up only one point from the previous two games against Sevilla and Real Betis.
Simeone knows there can be no let-up from his side in the battle to be crowned champions, with six games to go including a trip to Athletic Bilbao on Monday.
Real Madrid's 3-0 win over Cadiz on Thursday had temporarily nudged Atletico down to second place.
Atletico boss Simeone said: "LaLiga is very complex, we cannot relax, tomorrow we will take care of the Bilbao game."
He said: "There are four teams close to being able to close a great season, Sevilla are doing well, Madrid responded well yesterday and Barcelona are playing now.
"We are to think game by game and we are not going to change now. We think about the next game and we will try to move it forward."
Barcelona won 5-2 against Getafe in Spain's late match on Thursday, after Simeone held his post-game news conference, and Ronald Koeman's side remain very much in the title frame, with a game in hand and a home fixture against Atletico to come next month.
Simeone praised his players for the way they have reacted to slipping up against Sevilla and Betis.
"After Betis I said that the team was in a moment of resistance and is growing after that game," said the former Argentina midfielder.
Simeone reiterated that Atletico's withdrawal from a proposed European Super League was the right decision.
"The day before the decision was made, they already told us what was going to be discussed, it seems like a great decision to me." he said.