The game was deadlocked at 1-1 heading into the 80th minute before Gameiro scored a devastating hat-trick in the space of four minutes and 43 seconds - the fastest in La Liga since Bebeto's against Albacete in 1995.
The victory, which follows last week's come-from-behind 3-2 win over Celta Vigo, takes Atletico to within a point of third-place Sevilla in the table, prior to their match with Eibar later on Saturday.
And Simeone was thrilled with the fighting spirit shown by his side after the introductions of Gameiro, Saul Niguez and Thomas Partey added more shape to their line-up.
"The changes in the second half were decisive because they gave us balance in the middle of the pitch, and then the pace of Gameiro settled it," he said.
"We didn't expect anything different. This is a stadium where it's always been tough for us to win.
"I'm delighted for Gameiro because it's not easy to score three goals that were especially important for the team.
"In the last few minutes, as happened against Celta, we did some damage. The team knows how to react to conceding goals."