The Americans had reached five consecutive Gold Cup finals before this year.
In an action-packed match, the U.S. survived repeated waves of attack by Panama during both regulation and extra time to set up the penalty shootout.
Each team converted their first two penalties before Mejia stonewalled the Americans on their next three.
He made a diving stop to his right against U.S. captain Michael Bradley, then blocked DaMarcus Beasley's final attempt to end the match.
Panama made three of their first four attempts, with Harold Cummings scoring the last of them.
Appearing to be a much more motivated side coming into the contest, Panama took early control in regulation and after a scoreless first half, they went ahead 1-0 in the 55th minute on a goal by Roberto Nurse.
Clint Dempsey tied the game for the U.S. in the 70th with his seventh goal of the tournament. DeAndre Yedlin made a nice run into the box and played the ball backwards to Dempsey, who netted home on a diving strike.
From there, the Americans withstood constant attacks by Panama.
U.S. goalkeeper Brad Guzan, who before the tournament had made a career of backing up Tim Howard, did well to keep his team alive and finished with 11 saves.
Jamaica, who will appear in their first ever Gold Cup final, take on Mexico for the title at Lincoln Financial Field in Philadelphia on Sunday.
(This story corrects the score to indicate it was a shootout victory)
(Reporting by Jahmal Corner in Los Angeles; Editing by Mark Lamport-Stokes)
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