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Steve Gohouri's stoppage-time equalizer for Wigan relegated Hull from the Premier League after a 2-2 draw on Monday while Arsenal lost 2-1 at Blackburn for its fifth game without a win.
Leading 2-1 after goals by Will Atkinson and Mark Cullen, Hull looked set to take its relegation fight down to the final round of games before Gohouri scored with an acrobatic, overhead kick from close range.
The result means that Hull, promoted two seasons ago, cannot catch 17th-place West Ham and is relegated to the League Championship, along with Portsmouth and Burnley.
"It's a gut-wrenching way to lose. I thought we deserved three points," said temporary Hull manager Iain Dowie, who was put in charge until the end of the season after the club fired Phil Brown in mid-March.
"It's heartbreaking but I'm very proud of this display. It's a horrible feeling to lose that because we deserved the three points. But these things happen when you're down there. We come away from home and get two goals and not managed to take all three points."
Needing to win its final two games by big margins to stand any chance of staying up, Hull showed few signs of achieving that, although midfielder Kevin Kilbane fired a left-foot drive past the near post midway through the first half.
Victor Moses gave Wigan a 30th-minute lead when he cut in from the left, beat two defenders for pace and fired a low diagonal shot which went in off the far post for his first goal since his January move from Crystal Palace.
Atkinson equalized in the 42nd minute when he headed home a left-wing cross by Kilbane after Wigan goalkeeper Vladimir Stojkovic, who will be in goal for Serbia at the World Cup, had blundered by punching away a ball into the area instead of catching it. It appeared the goal had initially been ruled out by a linesman's flag but referee Phil Dowd gave it after consulting his assistant.
Cullen revived Hull's hopes of staying up by scoring his first goal for the club when he was left unmarked at the far post to head home a cross from George Boateng in the 64th minute.
Dowie's side looked set to hold on for victory but lost possession on a breakaway in midfield and the ball was fed back into the Hull area. Paul Scharner rose to head the ball into a crowded goal area and Gohouri scored to silence the visiting fans.
Arsenal chased a victory at Blackburn to guarantee finishing third, which would have sent it straight into the group phase of next season's Champions League, avoiding the qualifying rounds.
Arsenal striker Carlos Vela missed an open goal after only two minutes when he pulled a cross from Theo Walcott wide of the far post but the visitor went ahead through Robin van Persie's close-range header from Samir Nasri's cross.
David Dunn equalized in the 44th minute when a low cross by Keith Andrews was deflected into the path of the unmarked midfielder, who tapped the ball home for his 10th goal of the season.
Arsenal 'keeper Lukasz Fabianski made top-quality saves to keep out shots from Morten Gamst Pedersen and David Hoilett while Mikael Silvestre almost turned a flicked-on, long-range throw by Pedersen into his own net,
From the corner, however, Fabianski failed to get to the ball and Christopher Samba headed home from close range in the 68th minute.
While Blackburn's victory sent the team up three places to 10th, Arsenal can still be caught for third by either Tottenham or Manchester City, who each have a game in hand but play each other on Wednesday.
"I thought it was a poor football game overall," said Arsenal manager Arsene Wenger, who complained that Blackburn fouled Fabianski for both its goals.
"I thought both goals were not regular. Their main purpose every time is to stop the goalkeeper from playing the ball. He had no chance as a goalkeeper, he was pushed every time."
