The home side appeared to be heading for victory through Mathias Doumbe's first-half header, but Charlton turned the match on its head with two goals in five minutes late on from Kelly Youga and Andy Gray.
The Pilgrims responded with one final charge that saw Belgium international Mpenza score his first goal since joining Argyle at the end of the August transfer window.
The ex-Manchester City man, who has yet to start a game for his new side, volleyed home Rory Fallon's nod-down of goalkeeper Romain Larrieu's long punt out to keep the pressure on Charlton manager Alan Pardew.
Doumbe's first goal for the Pilgrims in three years, in the 37th minute, had seemed to have done enough to give Argyle a fourth home win of the season.
However, Charlton remained positive and levelled when Youga headed home Nick Bailey's 86th minute left-wing corner, although Larrieu felt he had been fouled in the goalmouth scramble.
Four minutes later, referee Andy Hall spotted Fallon's clear foul on Mark Hudson and Gray stepped up to fire home what now looked like the winner in front of 500 happy away fans.
Argyle manager Paul Sturrock threw on two attackers to bolster his side's slim chances of rescuing a point and one of them, Mpenza, came up trumps with a stunning right-foot volley.
Earlier, Larrieu had defied Charlton's best efforts to score, keeping out two Matt Holland efforts in the first half and making a tremendous stop to thwart Hudson in the second.
The Palace skipper was no more than eight yards from goal when Lloyd Sam's cross reached him, but the Pilgrims' French goalkeeper somehow got down to turn the powerful shot around his post.