Pena's blast staked the Rays to a 2-0 lead and Luke Scott added an RBI triple later in the frame for Tampa Bay, which evened its the four game series at one win apiece.
Matt Moore (6-6) allowed two runs on three hits and five walks over five innings, but earned the victory.
Josh Tomlin (5-6) absorbed the loss, surrendering four runs on seven hits through 5 2/3 frames.
Jason Kipnis and Jose Lopez each drove in a run for the Indians.
Former Titans kicker dies in car crash
UPI Sports Results for September 20, 2014