Fielding just six players with first-grade experience, the Panthers raced to a 22-6 halftime lead at Lecihhardt Oval before running out 38-22 victors.
Granted, Manly had also rested their big names, with the Trbojevic trio, Daly Cherry-Evans, Hamole Olakau'atu, Jason Saab and Taniela Paseka among those left on ice.
Still, the Sea Eagles had up to eight players in their team likely to feature in their round-one side against North Queensland.
And they were outplayed by the Panthers, whose top squad flew out for Vegas on Thursday ahead of their season opener against Cronulla.
Penrith's halfback Trent Toelau was particularly impressive, fooling Manly's defence with a dummy to score from 10 metres.
He also kicked twice for tries, once with pinpoint accuracy for winger David Fale and another through a grubber for Tom Jenkins.
Toelau played 12 NRL games off the bench for Penrith last season, and is low in the depth charts for a starting spot this season.
But he did show on Thursday night he had the potential to keep a cool head if called upon.
Fale also bagged two tries in the win, and cleverly intercepted a Tolu Koula ball in the lead-up to Jenkins' try.
For Manly, Lehi Hopoate was again their best for a second straight trial match, after being shifted from the wing to fullback early on after Clayton Faulalo suffered a head knock.
Siua Taukeiaho also showed some promise in his bid to play his first NRL match since 2022, having two stints and putting Ethan Bullemor through a gap to score.
