Defeat in north London would relegate Roberto Martinez's side three days after their stunning FA Cup final victory over Manchester City.
A draw would prolong their survival fight in theory, but only final-day victory over Aston Villa coupled with a Sunderland defeat at Tottenham - all with an 11-goal swing - would then keep them up.
Sky Bet make Wigan 1/33 to go down, but Martinez is hoping the memories of Wembley and of last April's win at the Emirates will inspire his players.
He said: "It's not just winning the FA Cup - although it's a unique moment in your career - it's also the manner in which we competed against such a talented football team. That gives you great confidence.
"We know we're going into another big final now, the way we see it is a final within the league competition playing against another top club in Europe.
"But we're playing in an environment where we were successful last season so we've got that picture in our heads."
Wigan have won their final two games in each of the past two seasons and secured safety on the final day in 2011.
Martinez said: "We're starting the fight for the final six points, which we always do in every season. That's the difference between achieving our aim and not, so it's nothing different."