Arsenal, meanwhile, is now primed to qualify for the Champions League for the 16th consecutive season after reclaiming fourth place and sitting a point above Tottenham with one match remaining.
Wigan, weary from Saturday's first-ever cup win, briefly posed a threat when Shaun Maloney cancelled out Lukas Podolski's opener just before half time from a free kick.
But the powerful start to the second half yielded nothing for Wigan as Arsenal's ruthlessness produced three goals in eight minutes.
Podolski scored his second, either side of goals from Theo Walcott and Aaron Ramsey, as Arsenal sent Wigan out of the topflight.
"We've had an incredible eight years in the Premier League and we have to take the good things from last few years, and there are many," Wigan manager Roberto Martinez said. "We'll bounce back as we always do at Wigan.
"We're on a fantastic financial footing, we have huge assets and a philosophy for the long term."
Despite winning many plaudits for their style of play under Martinez, Wigan has been unable to amass the points required for survival.
"It is sad that they go down because they are a good team, they play good football and are an intelligent team with good players," Arsenal manager Arsene Wenger said. "If they stay together they will certainly come up again."
Overlooking fears over fatigue, Martinez stuck with the same team that produced a first title in the club's 81-year history at Wembley Stadium by beating Manchester City Saturday.
But they struggled to replicate the dynamic performance that ultimately overwhelmed City.
"The FA Cup gave us a bit of hope to finish the season in the league on a real high, the youngsters came in and gave us a different sense of confidence," Martinez said. "It was great to win the FA Cup — that will live forever for the fans. Today is really disappointing but it is something we can rectify.
"It's a difficult time but it's time to look back, get stronger and prepare for the future."
Arsenal took just 11 minutes to take the lead, with Santi Cazorla exploiting gaping holes in the defence before picking out an unmarked Podolski, who headed into an open net from close range.
Wenger was furious when a free kick was awarded against them just before half time when Maloney went down under contact from Mikel Arteta.
Maloney sent the resulting free kick dipping into the net, with Wojciech Szczesny at full stretch getting a slight touch but unable to keep the ball out.
At the start of the second half Szczesny did manage to deny Wigan, coming off his line to block Arouna Kone's effort.
"We were not as fluent or as confident as we wanted to be," Wenger said.
They soon were.
A succession of chances fell to Arsenal after Walcott breezed down the right and cut the ball back to Cazorla, who was denied by Joel Robles. From the rebound, Tomas Rosicky could only sweep the ball wide.
The pressure was telling and Arsenal made the breakthrough again in the 63rd.
A low cross from Cazorla on the right reached Walcott in a central position and he nudged the ball over Joel, who had slid in studs-first from his goal-line but couldn't make the block.
Five minutes later, Podolski broke clear and raised ball into the net.
With Arsenal's cutting-edge finally showing, the energetic hosts compounded Wigan's misery.
Ramsey cut in from the left and lifted the ball into the roof of the net over the onrushing Joel.
Arsenal, having made its worst-ever start to a season since Wenger took charge in 1996, is now edging back into the Champions League going into Sunday's finale at Newcastle.
"It is all open, but it depends on our result. Even third place is not out of sight of we win the game," Wenger said.
"It took us some time to get going, but I believe mainly we didn't win the big games, especially at home. That is why it took us a long time to find a level of confidence and to balance the team as well because we had many new players."
Despite not seeing Arsenal win a trophy since 2005, the fans still stayed behind to cheer Wenger and his team after their final home match.
From jeers in October to cheers in May — the fans in the rain sang "There's only one Arsene Wenger."
Next week he'll become the longest-serving current Premier League manager when Manchester United's Alex Ferguson enters retirement.