It was Wilson’s first appearance since February 6, with the Magpies winless during the time their top scorer has been out with a hamstring problem, but it was Saint-Maximin who would do the damage at Turf Moor.
Within two minutes of his introduction, the Frenchman - limited to 18 league appearances this season through illness and injury - ran into the penalty area, drawing three defenders before pulling the ball back for Jacob Murphy to fire in an equaliser.
Bailey Peacock-Farrell, deputising for the injured Nick Pope in the Burnley goal, had enjoyed a relatively quiet afternoon to that point, but five minutes later he was picking the ball out of the net again as Saint-Maximin raced from the halfway line before finding the bottom corner.
It was a remarkable turnaround after Newcastle had been second best for almost a full hour, and one which could just transform their season.
Victory ended a seven-game winless run for Bruce’s side, and the second-half display offered a roadmap out of trouble.
But Sean Dyche must rue the three points that got away as his side, who have won just one of their last eight, let a winning position slip for a second week running.
For much of the afternoon they had looked in control against a Newcastle side short on confidence.
Ciaran Clark had come into the Magpies defence to covered for injured captain Jamaal Lascelles, but the Republic of Ireland defender hardly covered himself in glory as Burnley took a deserved lead with 18 minutes gone.
It was Clark’s poor header which went straight to Ashley Westwood, and when he played it forward to Chris Wood the New Zealand forward beat Clark for pace before pulling it back for Vydra to score his third goal in five, having needed the previous 53 outings to reach the same tally.
Newcastle stirred in response. Dwight Gayle, making his 100th league appearance for the Magpies, poked the ball into the net from an offside position - though it was closer than it first appeared given that Erik Pieters was down on the far side of the pitch.
Peacock-Farrell had been a spectator for much of the half but made a superb save to parry Gayle’s close-range header seven minutes before the break.
As the ball looped up, James Tarkowski went to boot it clear, catching Sean Longstaff in the head as he did so. VAR Stuart Attwell took a long look but ultimately agreed with referee Anthony Taylor that Tarkowski got to the ball first.
If Newcastle were aggrieved by that, they were also lucky not to be two down before the break, with Martin Dubravka reacting well to prevent a Paul Dummett own goal.
The second half started much as the first half had ended, with Dubravka tipping over shots from Matt Lowton and Dwight McNeil.
Bruce had seen enough, replacing Gayle and Joelinton with Saint-Maximin and Wilson, and the game quickly changed.
Burnley, stunned, tried to rally. Wood, looking for a fourth goal in four games, was teed up by Pieters but got his shot all wrong before Vydra fired into the side netting.
But it was Newcastle who came closest to adding to the scoring, and inevitably Saint-Maximin was the instigator again as he pulled the ball back for Miguel Almiron, whose shot was blocked by Tarkowski on the line.
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