Hull's first foray into Europe was ended by away goals as Belgian side Lokeren booked their place in the group stages of the Europa League.
Robbie Brady scored twice for the Tigers but Jordan Remacle's goal in between was enough to knock them out.
Brady struck after just six minutes to level the aggregate scores and added a penalty after 55 minutes.
But the Tigers had Yannick Sagbo sent off for a 71st-minute foul and could not get the third goal they needed.
Trailing 1-0 from the first leg of the play-off, Hull could not have made a better start against the Belgian cup holders as Brady bundled in a cross from Maynor Figueroa at the far post.
But Steve Bruce's side, which showed six changes to the team that had drawn with Stoke last weekend to extend their unbeaten Premier League start, failed to build on that and Lokeren threatened when Mijat Maric headed over following a 15th-minute corner.
|Born in Marseille, 12 April, 1988|
|Joined Hull from French club Evian in July, 2013 after starting career at Monaco|
|Sent off against Norwich City in his second appearance for Hull|
|Scored four times for the Tigers last season|
|Yet to appear in the Premier League this season|
David Meyler went close to doubling Hull's lead five minutes before the break with a volley from Sagbo's knock-down which forced Davino Verhulst into a fine save.
Still needing a further goal to advance, City then found themselves behind again in the tie four minutes into the second half.
Goalkeeper Allan McGregor, who had been at fault for the goal which had given Lokeren a first-leg lead, made a decent save from Killian Overmeire's fiercely struck free-kick.
But from the corner that followed, Remacle blasted in an angled shot which left Hull needing to score twice to progress.
Brady gave them a glimmer of hope when he scored from the spot following a handball just six minutes later as visiting manager Peter Maes was sent from the dug-out for his protests.
But when Sagbo was dismissed for a challenge on Georgios Galitsios with 20 minutes to go the momentum drained from the home side.
Bruce is looking to sign a new striker before the transfer window closes and Hull's lack of firepower was apparent as Lokeren comfortably held on, bar a late scare when a shot from substitute Tom Huddlestone was blocked on the line.
Hull manager Steve Bruce: "To go out the way we did is the worst, on away goals, but that's what playing in Europe is like. It's a totally different ball game and we didn't get to grips with it.
"To have had a big couple of European nights would have been terrific so it's a shame. It would have been a great adventure for everyone.
"We've won the match and gone out on the rule, but if we're being honest we didn't play to the levels I expect.
"That's the disappointing thing, even though we won the game. It's gone too quick for everyone but it's not to be, so we move on."
- 2RoseniorBooked at 44minsSubstituted forJelavicat 66'minutes
- 5ChesterSubstituted forInceat 75'minutes
- 7MeylerSubstituted forHuddlestoneat 75'minutes
- 27El Mohamady
- 20SagboBooked at 71mins
- 24AlukoBooked at 79mins
- 30VerhulstBooked at 86mins
- 8PersoonsBooked at 74mins
- 7OvermeireBooked at 64mins
- 19Dutra JuniorSubstituted forLeyeat 76'minutes
- 14RemacleSubstituted forNgolokat 88'minutes
- 29de PauwSubstituted forMertensat 90'minutes
- 6Ricciardi Oyama
- Ovidiu Hategan