Evan Longoria was hit by a pitch from Jason Grilli (1-2) to start the bottom of the 10th and went to second when Ben Zobrist walked. Pena then hit a liner to center to score Longoria.
Pena finished with four RBIs for the Rays, who remain three games behind AL wild-card leading Boston. The Rangers fell two games in back of the Red Sox, who beat the New York Yankees 14-1.
Pena has three of his 16 career multihomer games this season, and has eight homers over his last 14 games.
Grant Balfour (5-2) struck out two during a scoreless 10th for the win.
Marlon Byrd had pulled the Rangers even at 4 on a two-out, ninth-inning solo homer off Tampa Bay closer J.P. Howell.
Pat Burrell hit a go-ahead RBI double in the eighth as the Rays took a 4-3 lead. His drive off the left-field wall scored Pena, who drew a two-out walk from C.J. Wilson.
Michael Young homered and had his third straight three-hit game. He has 18 three-hit games this season and 144 in his career, which is three behind teammate Ivan Rodriguez's club record.
Pena hit a solo homer in the second and put the Rays up 3-2 on a two-run shot during the fourth.
Texas went ahead 2-1 in the third when Taylor Teagarden drove in a run with a double and Young had an RBI triple. Young tied it at 3 on a sixth-inning solo homer.
Tampa Bay's Matt Garza allowed three runs and six hits over seven innings. He has just one win in his last nine starts.
Rangers right-hander Tommy Hunter gave up three runs and seven hits in five innings.
Young singled in the first to extend his hitting streak to 10 games. He has 19 career double-digit hitting streaks, which ties the Rangers mark held by Rodriguez.
NOTES: The AL East-leading Yankees had a group of scouts, including Bill Livesey, Rick Williams and Joe Caro at the game between playoff contenders… Longoria hit into his AL-leading 23rd double play this season in the third. … Byrd has 13 RBIs over his last 13 games. … The Rangers activated Grilli (right elbow) from the 15-day disabled list before the game and optioned RHP Willie Eyre to Triple-A Oklahoma City. … Texas RHP Brandon McCarthy (right shoulder) made his fourth minor league rehab start for Oklahoma City.