The central midfielder, whose header delivered an improbable FA Cup triumph for Latics last May, left the DW Stadium in an ambulance amid fears of a second broken leg in 15 months.
He was involved in a full-blooded first-half collision with Tykes midfielder Martin Woods and, while there appeared to be no malice, the damage is likely to be serious enough to prevent Watson from replicating his cup heroics against Manchester City in their forthcoming quarter-final.
There were a few worried expressions etched on Wigan faces after that incident, but they focused on the task in hand with on-loan strike duo Nicky Maynard and Martyn Waghorn both scoring in the first half.
It proved enough, even if the hosts were below par after the interval, to lift Uwe Rosler's team to seventh, four points behind Reading with a game in hand.
The last time Barnsley visited this stadium was 11 years ago when a Latics team including a teenage Leighton Baines lifted the old Division Two trophy.
Plenty of positives have happened for Wigan in the intervening decade time so, while that afternoon in 2003 was a cause to celebrate reaching the second tier, this division is one Rosler's side are now intent on departing at the top end.
Given the form of the current top six and, with the Latics playing catch-up due to their earlier European excursions, they could not afford to slip up in games like this.
Rosler had banned talk of the mouthwatering FA Cup quarter-final draw against a club where he enjoys cult-hero status on Monday, insisting his focus was purely on the Tykes, and his players seemed to heed the notice. Jean Beausejour and James McClean brilliantly worked an opening down the left yet the latter's cross was drilled in with too much pace.
Nick Proschwitz narrowly headed over, despite being unmarked, at the other end before a fully-committed collision between Watson and Woods left both men down in pain.
It quickly became apparent that Watson, the symbol of Wigan's cup exploits both this term and last, was in serious trouble, as displayed by Chris McCann's worried face and the oxygen mask which the midfielder needed.
Watson was eventually taken off on a stretcher after a four-minute delay, but his team-mates were soon able to train their concentration back to the contest.
The hosts were enjoying plenty of success down the left flank and it was no surprise that Maynard's opener came from Beausejour's cross in that region, with the Cardiff loanee given ample time to slot home his third goal in two games 10 minutes before the break.
The Tykes did little to prevent Wigan's joy down the left and they were two goals down nine minutes later when Waghorn netted for the first time in Latics colours from McClean's pinpoint delivery.
Visiting boss Danny Wilson introduced Lewin Nyatanga and Brek Shea at the interval and Barnsley had opportunities to halve the deficit, Woods firing a half-volley over and both Jim O'Brien and Emmanuel Frimpong going close with free-kicks.
Wigan had completely eased off the accelerator, much to Rosler's annoyance, yet their opponents were wasteful, Dale Jennings, Shea and Proschwitz, twice, all missing the target in an uninspiring second period.