The Owls were unchanged from the side which beat Wolves last weekend, meaning winger Adam Reach filled in at left-back with Daniel Pudil on the bench.
Preston included former Owls loanee Aiden McGeady, who had an unsuccessful spell at Hillsborough last season.
The Owls nearly made the perfect start and twice Reach was involved.
First, his long pass picked out Fernando Forestieri, who chested it down but could not find power to test Chris Maxwell in the Preston goal.
Then in Wednesday’s next attack, Reach drove forward again and this time picked out Lucas Joao, who turned well but the ball ran away from him and the chance was gone.
The goal the hosts had been threatening came in the ninth minute and again Reach was prominent. His shot was going wide until Forestieri glanced it home with a deft header.
Callum Robinson replied for Preston, his long-range effort smashing against the post.
The Owls were forced to make two early changes, when Ross Wallace limped off on 27 minutes to be replaced by loanee Will Buckley.
Then Glenn Loovens was forced off, David Jones coming off the bench, as Carlos Carvalhal was forced to juggle his line-up.
The Owls should have been 2-0 up just before the break, when Buckley somehow spurned two golden chances.
He broke clear, but with only the goalkeeper to beat, opted to pass to Forestieri but his ball was poor.
Then when Forestieri crossed back into the box, Buckley was free at back post but somehow headed wide.
Buckley had the ball in the net at the start of the second half, but it was ruled out for offside, as the Owls pushed for a second.
The Owls were reduced to 10 men when Forestieri was sent off for an off-the-ball incident.
Preston had three dangerous free-kicks, but failed to test Keiren Westwood.
And the Owls doubled their advantaged when Buckley was flattened by Maxwell, and substitute Steven Fletcher converted from the penalty spot.
Preston pulled a goal back on 81 minutes when substitute Eoin Doyle netted - when the Owls were down to nine men as Buckley received treatment on a shoulder injury.
But the visitors finished with nine men when both Doyle and Jermaine Beckford were sent off for fighting with each other.
Owls boss Carlos Carvalhal said: “We deserved to win this game, for sure. In the pre-match, I said Preston are a tough team to beat, they play very compact and are very organised.
“They won at Norwich, they drew with Brighton so we knew we must play well to win this game.
“We started well and got the goal and I have to say, the attitude of the players was fantastic as we picked up three separate injuries.
“We lose Ross Wallace, Glenn Loovens and Will Buckley and we had to see the character of the team to win the game.
“It was a difficult game and we deserved to win.
“I did not see the incident with Fernando so I cannot really say but I am told the decision was correct.
“I saw what happened with the two Preston players and, of course, this helped us because it meant the game was very close to being over.
“The most important thing is the points, which we have. We must wait for the reports from the doctor but we have no issues because we have a very good squad and players who can come into the positions if necessary.”