The Tigers had lost five times and drawn twice on their previous seven visits but this time Abel Hernandez made it eight goals in his last eight Championship games to set Hull on their way to their first win at the ground since 1986.
Mohamed Diame set up the goal with a deflected through ball and Hernandez repaid the compliment by setting up his strike partner for the second.
Hull chief Steve Bruce made just one change from the side which lost 1-0 at Burnley, bringing Tom Huddlestone into central midfield to partner Jake Livermore.
Blackburn captain Grant Hanley (shoulder) and former Tigers loanee striker Danny Graham (hamstring) were ruled out of the game so Shane Duffy returned in central defence and Simeon Jackson was paired with Tony Watt up front for his first start for Rovers. Hope Akpan was also a late withdrawal through illness so Craig Conway came into central midfield.
Former Hull player Corry Evans was Blackburn’s sitting midifled man in a 4-1-2-1-2 line-up.
Hernandez had a couple of early chances, volleying wide before striking against the post after a scuffed shot against Diame rebounded into his path - his partner being flagged offside in any case.
Right-back Ben Marshall was allowed too much space to cut inside and test Allan McGregor in Blackburn’s first attack of note.
A quiet spell followed before Diame showed great skill in beating two men as he came in from the left before curling a shot narrowly over.
Odubajo did well to block from Darragh Lenihan for a corner and the first half ended goalless.
Hernandez and Sam Clucas both fired wide before the former gave Hull a 53rd-minute lead, sidestepping goalkeeper Jason Steele and tapping home from inside the area after Diame had fed the ball down the middle off Elliott Ward following a break involving Livermore and Robert Snodgrass.
Blackburn responded and Andy Robertson cleared off the line at the far post from Ward as Rovers forced three successive corners.
Pressure was eased as Hull made it 2-0 in the 63rd minute, Hernandez drawing Steele to leave Diame with a simple tap-in after Huddlestone’s clever chip over the top of the defence had sprung the offside trap.
Hernandez was rested as Chuba Akpom entered the fray and should have made it 3-0 only to be denied by Steele’s close-range block after a great run and supply from Robertson.
McGregor kept it 2-0 by beating away Marshall’s fierce drive and a volley from Evans.
Hull manager Steve Bruce said: “I thought we looked a very good team today and it was a good performance from everybody. We’ve missed two or three chances late on which could have improved our goal difference but we thoroughly deserved the win in my opinion.
“I thought we were playing within ourselves in the first half and wanted us to go and express ourselves and take the shackles off. We knew we had more in the tank and I thought in the second half we gave a very good performance where we could have scored three or four.
“That’s as good as we’ve played for a long time.”
Hull could be pushed down to second place on Monday, with Middlesbrough able to reclaim top spot by beating Leeds.
Tigers manager Bruce did not want to single out players but in Hernandez he knows he has a player who can provide the platform to promotion.
And after the Uruguayan’s eighth league goal in the last eight league games, Hull’s manager expects him to improve further.
“I think he’ll get better when the weather gets better and it gets a bit warmer. He seems to enjoy the sunshine,” Bruce said. “He had a tough time last year in terms of the Premier League but he looks a very good player and let’s hope he takes us where we want to be.
“He’s a goalscorer and is doing very well at the moment.”