USA played out a goalless draw with Wales in its first game for nine months last Friday (AEDT) but had no trouble converting its chances at Stadion Wiener Neustadt.
Fielding their second-youngest starting XI ever at 22 years and 154 days old on average, made up entirely of European-based players, Gregg Berhalter's charges got off to a slow start as Jose Fajardo glanced in the opener from Panama's only on-target attempt of the first half.
Reyna, making his second appearance just three days after his 18th birthday, levelled up with what was also his side's first direct free-kick goal since Jozy Altidore netted against Jamaica in the 2017 Gold Cup.
Nicholas Gioacchini was next to get off the mark for USA on his full debut with a tap-in after Ulysses Llanez's shot was parried into his path.
He had his second of the game four minutes later with a header inside the six-yard box, making him the fifth different USA player to score multiple goals in their past seven matches.
Gioacchini squandered a chance to complete his hat-trick when his spot-kick was saved by Orlando Mosquera and Fajardo then appeared to set up a nervy finale when powering a shot past Zack Steffen 11 minutes from time.
Sebastian Soto killed off any hopes of a comeback with a goal five minutes and 46 seconds after being introduced for his debut and he doubled his personal tally in added time, scoring his brace either side of Sebastian Lletget's strike.