In Narcis Pelach's debut game in charge, Ben Wilmot scored to put the Potters ahead. However, three quick goals in just 17 minutes secured Tim Walter his first victory as Hull boss.
Kasey Palmer nodded in the equaliser on his first Tigers start, following up after his penalty had been saved by Viktor Johansson, before substitute Regan Slater and a Wilmot own goal completed the turnaround.
Walter's men arrived in Staffordshire without a win to their name, having scored just two goals in their first five league outings.
The Tigers had the lion's share of possession in the first half but failed to create any clear-cut opportunities. Mohamed Belloumi fired over twice in the early stages, while Palmer lifted a free-kick over the crossbar.
TrendingStoke had started much the brighter side after appointing former Norwich coach Pelach to replace Steven Schumacher, who was relieved of his duties following 11 wins in 29 league games.
Jun-Ho Bae fired wide when he was picked out by Million Manhoef inside the area before Lewis Koumas also flashed a shot wide within the first 10 minutes.
Manhoef drew the first save of the evening when Ivor Pandur was forced to push his left-footed effort away from danger.
From the resulting corner Wilmot met Bae's corner and crashed a header past Pandur a year to the day since his last Potters goal against Huddersfield.
Manhoef missed a golden opportunity to double the lead before half-time after clever movement from Tom Cannon.
The Leicester loanee drew a defender away for the Dutchman to have a free run at goal before he scuffed his effort into the advertising hoardings.
Hull were given the opportunity to equalise just past the hour mark when Belloumi was brought down by a clumsy challenge from Eric Bocat.
Palmer's spot-kick was brilliantly saved by Johansson, who dived down to his right, but the Swede could do nothing about the follow-up as Palmer headed in his first goal since his deadline-day move from Coventry.
Wilmot then played the ball into the path of substitute Liam Millar and the winger picked out fellow replacement Slater to lash his effort beyond Johansson.
Wilmot's miserable second half was complete two minutes later when he diverted Palmer's cross into his own net beyond the despairing Johansson, who was unable to prevent the ball dribbling over the line, to condemn Stoke to a fourth defeat in five.
Stoke's Narcis Pelach:
"We lost control in the second half. I would say at the end of the first half as well, we started to lose control. We looked out of energy, I could see some things of new style of working to do, defending the space. But we gave them a lot of possession. We had to be more on the front foot.
"But it's just today, we will try to be more solid, to make the team more compact. It went that way, so I'm looking forward to the next week to try to train more and be more aggressive.
"The penalty, I think it was one. It's a big moment, we didn't take our moments in the game. We had a big chance for 2-0 and then it's 3-1. If we take it, it's a different story. We shouldn't have lost, but then the game changed.
"We were affected from the [first] goal. We all saw that. We have to be stronger mentally. Something is always going to happen in games, so we have to try to accept it and try to go into the next action. We saw some things that we started to implement, but it's a long season and we have to keep working and try to get better."
Hull's Tim Walter:
"It's hard to describe because I never had that feeling before, I've never not had a win after five games. For me it's a new situation, I also knew the whole time we could win all the games in the last weeks.
"Tonight we did it, that's why I'm really proud of my boys. They deserved to win, we didn't concede so many chances against us.
"After conceding the goal, we were better in the game. We were more proud to play forward, more courageous. We showed more bravery over the whole game, that was the key to the result.
"It's a first win, let the church into the village. All we have to do is keep working, that's my key principle: I always want to work and develop my players, improve them and try to put them into the best performance. That's the key, they believed it."