The Everton loanee was enduring a tough afternoon, passing up a host of opportunities and having numerous penalty appeals turned down.
But referee Karl Evans finally obliged after Vaughan took another tumble with 15 minutes remaining, and the striker made no mistake from the spot.
Vaughan and Neil Danns should have put Palace out of sight before the latter finally fired them ahead after half an hour.
But the Eagles dozed off just before the interval to allow Marlon Harewood to convert a rare chance for Barnsley and net his third goal since joining on loan from Blackpool.
The one-way traffic continued in the second half but Luke Steele kept Palace at bay until Vaughan snatched the points.
Palace almost took the lead after 15 minutes when Nathaniel Clyne's weak shot was fumbled by Tykes keeper Steele.
The ball fell to Darren Ambrose, whose scuffed effort bounced to Danns but the midfielder could not turn it in from all of three yards out.
Vaughan was looking lively and he ran onto a fine pass from Kemy Agustien and outpaced Paul McShane only to shoot wide.
Vaughan claimed he should have had a penalty after 22 minutes when he was sent sprawling in the area but referee Evans did not agree.
Ambrose then went on a marauding run down the flank and crossed for Vaughan but again the striker's header flew the wrong side of the post.
But Barnsley eventually caved in when Danny Haynes gifted the ball to Danns in midfield and he was allowed to stride forward to the edge of the area and ping a left-footed shot into the corner of the net.
However, against the run of play, the Tykes forced an equaliser before the interval.
Julian Speroni pulled off a fine save to keep out a shot from Jacob Butterfield, but he could do nothing moments later when Harewood got in behind the back four and coolly sidefooted Jason Shackell's pass across the Palace keeper into the net.
Vaughan was feeling aggrieved again after the break when he appeared to be shoved to the ground in the area, but again Evans was not interested.
Danns thought he had doubled his tally with a rasping drive that looked destined for the top corner but Steele pulled off a stunning save, and the keeper repeated the trick from Vaughan's point-blank header.
But when Diego Arismendi climbed on Vaughan's back in the box, the referee finally pointed to the spot and Vaughan did the rest.
Danns was denied again by the post after a mazy run, but the Eagles had Speroni to thank for securing the points with a fine save from Martin Devaney late on.
Crystal Palace 2-1 Barnsley: Match Report - view commentary, squad, and statictics of the game as it happened.