Boro have struggled on their travels this season and that looking like continuing when Billy Jones headed the home side in front after 27 minutes.
However, Leroy Lita produced a superb run and finish to draw Boro level three minutes later before putting the visitors in front just before the hour mark.
David Wheater, who has been linked with a move away from Middlesbrough in the January transfer window, then capped a fine performance by heading a third soon after.
The victory moved Boro one point clear of the relegation zone. Meanwhile, Preston stay bottom of the table, five points behind Boro.
Preston made a bright start and fashioned the first meaningful chance with 10 minutes gone when Jon Parkin laid the ball into the path of Darel Russell, who fired over from 20 yards.
Moments later Lita was dispossessed and Preston broke at pace with Michael Tonge playing the ball a little wide to Adam Barton who flashed a shot just wide of the post.
The game opened up and the dangerous Marvin Emnes got away down the left before providing a fine ball into the box but Lita was unable to connect properly.
Lita thought he had put the visitors in front soon after but his goal was disallowed for a foul.
With 26 minutes gone Middlesbrough goalkeeper Jason Steele produced a fine save to keep out a 25-yard effort from Russell.
But from the resulting corner, Danny Pugh picked out Jones at the far post and he headed in from close range to put Preston in front.
Middlesbrough had lost every game this season in which they have gone behind, but three minutes later, Lita embarked on a fine run from the halfway line and burst towards the edge of the box before blasting a shot high into the net.
The visitors ended the half the stronger of the two sides and began the second half in the same vain with Gary ONeil crossing for Lita, who headed wide.
Emnes was denied by a good block from Ritchie De Laet before Boro deservedly went in front with 59 minutes gone.
Julio Arca sent a long ball over the Preston defence and Lita raced clear before finishing well past Andy Lonergan for his second of the game.
It got worse for Preston two minutes later when O'Neil swung in a free-kick from the right and Wheater climbed highest to head home.
Preston never looked like getting back into the game and Lita could have had a hat-trick with eight minutes remaining - but he fired wide when clean through.