Former Reds academy player Jordan Clark returned to haunt his boyhood club by striking a late winner at Oakwell.
Hoyland lad Clark struck in injury time to earn The Shrews a 2-1 win.
The visitors took the lead through an Adam Davies own goal following a goalmouth scramble from a corner.
Sam Winnall ensured Barnsley went back in level by firing in on the turn.
New Reds strikers Michael Smith and Simeon Jackson started on the bench as head coach Lee Johnson again favoured playing Winnall alone up front.
Shrewsbury threatened early with Clark making a lively start.
He set up Tyrone Barnett for the first shot and then Lawrence's corner was headed over by Abu Ogogo.
Conor Hourihane fired a shot wide at the other end before Barnsley fell behind on seven minutes.
Another Lawrence corner was not properly cleared and was eventually bundled over the line with Davies getting the final touch after both Mark Ellis and Marc Roberts had helped the back goalwards.
The Reds responded well to going behind and Hourihane almost had them level but his curling effort rebounded off the post.
Marley Watkins then latched onto a Crowley pass and had two chances at the back post to level up the scores.
He tried to feed Winnall with the first but the ball rebounded to him and his shot was cleared off the line by Mark Ellis.
They levelled on 38 minutes when Winnall found space on the edge of the box and powered a shot beyond Jayson Leutwiler.
Shrewsbury had chances to go back ahead with Clark and Junior Brown both firing off target.
Michael Smith was introduced for his debut on 70 minutes with Winnall dropping into a deeper position in support of him.
Jean Louis Akpa Akpro looked the substitute most likely to score though and missed two chances to steal Shrewsbury the points.
In the dying stages Clark's clever effort went just wide of the post but he was not to be denied and fired past Davies well into injury time.
Barnsley: Davies, Wabara, Mawson, Roberts, Nyatanga, Scowen, Pearson, Hourihane (Harris 70), Crowley (M Smith 70), Watkins, Winnall.Unused subs: Townsend, Rothwell, G Smith, Jackson, Bree.
Barnsley were drawn away in the second round of the Johnstone's Paint Trophy. They will travel to Bradford City at a date on the week commencing October 5.
