The Owls created the first big chance, when Adam Reach sent a lofted pass forward to Forestieri, who controlled the ball with his chest and drove to the edge of the box, but his shot was straight at goalkeeper Chris Maxwell.
Forestieri continued to cause the visitors problems when he had a goal-bound effort blocked by Alex Baptiste, but he failed to clear the ball and Kieran Lee’s cross found Reach in space. The left-back’s mis-timed shot then bounced favourably for Forestieri, who finished expertly with a headed flick into the bottom right corner, from the centre of the box.
Callum Robinson went close to levelling the scores instantly, when he fired a shot against the post from just outside the area.
Wednesday then suffered a double injury blow. Firstly, Ross Wallace was forced off in the 27th minute with Will Buckley replacing him. David Jones then came on for captain Glenn Loovens, after he had gone down for treatment twice, before finally leaving the field in the 35th minute, passing the armband to Tom Lees.
Preston continued to create chances but failed to convert them, with Westwood comfortably saving two efforts from Alan Browne.
At half-time, Browne was substituted along with former Wednesday player Aiden McGeady, as Preston manager Simon Grayson introduced Marnick Vermijl and Jermaine Beckford.
Preston had several set-piece opportunities from just outside the box after the break. Beckford had one effort disallowed for taking it too quickly, while Robinson and Daniel Johnson saw their shots miss the target.
Goalscorer Forestieri was sent-off by referee Scott Duncan in the 65th minute following an off-the-ball incident.
The home side then suffered their third injury, when Lucas Joao took a knock and was replaced in the 74th minute by Fletcher.
Keeper Maxwell brought down Will Buckley inside the area and Fletcher made an immediate impact, side-footing the ball into the bottom right corner to double the hosts’ lead with just over 10 minutes remaining.
With Buckley off the field receiving treatment, Preston capitalised on their two-man advantage, when substitute Doyle (82) smashed the ball past Westwood into the left side of the net from close range.
With Preston failing to convert their chances, frustration spilled over and the referee brandished straight red cards to Doyle and Beckford – both for violent conduct – in the 90th minute.