Wesser played a brilliant hand against his former teammates, scoring a try in the 12th minute as South Sydney ran in nine tries to one.
Winger Junior Pia Kilifi was the only scorer for the Panthers, crossing for a four-pointer in the second quarter.
South Sydney's Fetuli Talanoa finished with a double while outside back Colin Best also scored a try on debut. Issac Luke, Jamie Simpson, John Sutton, Shannon McPherson and Shaun Corrigan also scored.
Souths fielded the strongest of the two sides but were still impressive with five-eighth Sutton and half-back Chris Sandow controlling the ruck throughout the contest.
Penrith split their squad into two, with the other half of their team going down to the Parramatta Eels 34-12 in Griffith.
Panthers coach Matt Elliott was satisfied with the performance, knowing he will put a much stronger outfit together for next week's NRL trial against Parramatta at CUA Stadium.
The Eels fielded Kiwi stars Krisnan Inu and Nathan Cayless and were expected to outclass the Panthers side that was made up of a number of under-20 players.
Former Manly half-back Jeff Robson was solid for the Eels, combining well with five-eighth Kris Keating, both players scored tries in the opening half. Forwards Todd Lowrie and Tim Mannah also scored in the first half.
The final two quarters were much closer as rookies Greg Nichols, Nathan Gardner and Jeremy Latimore scored for the Eels, while Luke Clydesdale finally put the Panthers on the board with a try in the third section. Tim Glasby added a second try for Penrith in the closing stages.
MORE NRL TRIALS INFORMATION: CLICK HERELike