Alex Neil’s side had beaten Sunderland and Leeds in the seven days prior to their trip to Teesside, and they claimed another notable scalp as their surge up the table continued.
Michael Rose’s early headed effort from a corner opened the scoring, with Mehdi Leris adding a second goal with an angled finish shortly before the interval.
Middlesbrough struck the crossbar through a long-range strike from Josh Coburn, but Michael Carrick’s side delivered an off-colour display as they suffered a first defeat since mid-September.
Stoke were the better side from the off, with Dwight Gayle coming close to opening the scoring in the second minute when he latched onto Luke McNally’s floated through ball, only to scuff his effort at goal.
Six minutes later, however, and the visitors were claiming the lead as the Middlesbrough defence failed to deal with a corner.
Sead Haksabanovic delivered the ball from the right, and after peeling off Matt Crooks, Rose found the net with a near-post header.
Seny Dieng might well feel he should have done better, with the Middlesbrough goalkeeper getting his hand to the ball but only succeeding in helping it into the net.
Stoke remained the dominant force and almost doubled their lead on the quarter-hour mark when Leris’ one-two with Ki-Jana Hoever sent him racing towards the edge of the 18-yard box, only for his tame shot to be saved by Dieng.
Haksabanovic threatened midway through the first half, firing a shot wide from 20 yards after Josh Laurent flicked the ball into his path, and Stoke’s superiority was rewarded with a second goal eight minutes before the break.
Daniel Johnson rolled the ball into Leris’ path on the right of the area and the Algeria international drilled a slick low finish into the far corner.
Boro had not created anything of note at that stage, but they finally sparked into life through Coburn shortly before the interval.
The youngster fired in a shot that was saved by Stoke goalkeeper Jack Bonham before hammering another long-range effort against the crossbar after picking up a loose ball and driving towards the edge of the box.
Jonny Howson fired a shot wide as the home side tried to rally at the start of the second half, but Stoke almost scored a third goal when Gayle teed up Haksabanovic in the area, only for Dieng to save the Celtic loanee’s side-footed shot.
Stoke’s clean sheet was confirmed with four minutes remaining when Bonham got down to produce an excellent save as he turned substitute Morgan Rogers’ flicked effort around a post.