Andy Keogh opened the scoring in the fifth minute and David Clarkson struck twice in the second half before substitute Brett Pitman added a late fourth as the Robins ran out emphatic winners.
The result left Brown still searching for his first victory since taking the helm at Deepdale and was another major blow to his side's hopes of avoiding relegation to League One.
To make matters worse, rookie defender Conor McLaughlin suffered a suspected broken leg in the first half.
The teenage right-back was hurt in a tackle in the 41st minute and was eventually carried off on a stretcher after lengthy treatment.
Brown gave striker Eddie Johnson his debut after signing from Fulham on loan late on transfer deadline day, while there were returns to midfield for Adam Barton and Darel Russell.
Martyn Woolford was handed his City debut following his arrival from Scunthorpe but Preston went close inside the second minute when Johnson fired over the bar from 12 yards out.
Moments later Keogh tried his luck from 25 yards only to see his effort blocked by McLaughlin.
Clarkson then dragged a shot wide of Andy Lonergan's goal but moments later the visitors led when Keogh collected a pass from Steven Caulker and hit a right-foot shot into the net from 12 yards.
Preston's Billy Jones then sought to find an immediate response but his 25-yard shot missed the target.
City goalkeeper David James was called into action in the 16th minute when he saved from Russell and three minutes later Preston went close again.
Leon Clarke crossed dangerously and Johnson greeted his delivery with a header from 12 yards that flew wide of the mark.
Yet North End continued to probe and in the 23rd minute Nathan Ellington sent a superb right-footed shot from 18 yards which drew a brilliant save from James who tipped the ball round the post.
From the subsequent corner by Barton, Sean St Ledger headed over from six yards out.
Ellington was similarly wasteful moments later when he headed wide from six yards and Ellington then had a shot tipped round the post by the impressive James.
Johnson fired over and Preston were dealt a blow on the stroke of half-time when McLaughlin was replaced by Wayne Brown.
Clarkson was a lively figure for City and headed over in the 53rd minute but he made no mistake three minutes later when he nodded in a left-wing cross from Pitman.
Preston tried to respond but Ellington headed over and in the 65th minute City had their third when Keogh's shot was parried and Clarkson swept home the rebound from 12 yards out.
Pitman added a fourth in the 85th minute when he collected a pass from Woolford and drove home right-footed from 18 yards.