Wigan's eight-season tenure in the Premier League came to an end as they were hammered at Arsenal, who moved back into the Champions League places.
Lukas Podolski headed the Gunners in front early on before Shaun Maloney's free-kick levelled the game.
Realistically Wigan had to win to keep their survival hopes alive.
But Theo Walcott's low strike, a lobbed second from Podolski and Aaron Ramsey's angled strike ensured Wigan will be playing in the Championship next term.
Arsenal are now fourth - a point ahead of Tottenham with one game to go and the Gunners know a win at Newcastle on Sunday will guarantee a place in next season's Champions League.
Wigan's defeat also means that Sunderland and Aston Villa can now also rest easy heading into the final weekend.
All the pre-match debate was about how well Wigan could recover from their historic FA Cup win over Manchester City just three days earlier, but manager Roberto Martinez picked the same starting line-up at the Emirates Stadium.
It was clear in the early stages that there were some weary legs and Arsenal were keen to capitalise, creating a chance for Santi Cazorla, who headed wide from Walcott's cross wide.
It seemed more mental fatigue than physical tiredness that gifted Arsenal the opener.
Podolski easily outmuscled James McArthur in the area and as the rest of the Latics defence stood still, the Germany international had a free header to turn in Cazorla's floating corner.
The Gunners were posing the biggest threat as they whizzed the ball around in Wigan's half with Kieran Gibbs almost getting on the end of a misplaced Bacary Sagna shot.
"Believe" has been Wigan's mantra in recent weeks and despite Arsenal's pressure, the visitors kept trying to hit on the counter-attack.
Maloney went down under what seemed like little pressure from Mikel Arteta and referee Mike Dean gave the Latics a chance as the referee pointed for a free-kick just outside the area.
The forward then managed to get the ball up and over the wall to beat Wojciech Szczesny despite the Gunners keeper getting a hand to the ball.
Wigan seemed to have cast aside their earlier stiffness and after the break only a good save from Szczesny denied Arouna Kone at close range.
If Martinez's side needed a reminder of Arsenal's threat, it came when Walcott played a ball across the face of goal for Cazorla and Latics keeper Joel Robles was forced into a double save before Tomas Rosicky's skidding shot went wide.
Arsenal regained the lead through Walcott after a superb low cross from Cazorla was turned home by the England forward despite Robles getting something on the ball.
The floodgates then opened as Wigan's weariness returned.
Paul Scharner played Podolski onside to allow the German forward in to lob over Robles before Ramsey fired in from a tight angle to complete the win that turned Wigan's tears of joy from Saturday into tears of anguish.
And in failing to keep their hopes of staying up alive, Wigan became the first team to win the FA Cup and suffer relegation from the top flight in the same season.