Atletico struggled to break down a stubborn Athletic at the Wanda Metropolitano before Simeone turned to Gameiro as his second substitute, taking off Koke and reconfiguring his side's attack.
Gameiro subsequently repaid his boss with a goal and an assist, scoring from a pass from fellow French forward Antoine Griezmann before setting up Diego Costa to wrap up the points.
The 30-year-old has a knack for providing game-changing moments on February 18, having hit a five-minute hat-trick in a 4-1 rout of Sporting Gijon on the same date a year ago.
Atletico have now won five straight games in all competitions, with Gameiro on target in a 4-1 defeat of Copenhagen at Parken Stadium in the Europa League on Thursday.
And with Atleti cutting Barca's cushion back down to seven points with 14 fixtures still to play and a trip to Camp Nou coming next month, Gameiro insists the title race is alive.
"It's a good day for us, we've won and we're still strong," he told beIN SPORTS. "We must continue like this.
"We will not stop, we know that we are playing well in this moment and we have to enjoy it."
Simeone had called for Atletico's fans to show more support for Griezmann, who gestured silence to them by putting a finger to his lips late in a 1-0 win over Valencia earlier in the month.
Gameiro backed his compatriot, who was influential in the Copenhagen victory by scoring a brace to give Atleti a foot in the last 16 of the Europa League.
"It's good for him and the team," Gameiro added. "The team is with him because he is a magnificent player."