Arsenal scored three times in eight second half minutes to go within a win from a 16th consecutive season in the Champions League and condemn FA Cup winners Wigan Athletic to relegation after eight seasons in the Premier League.
Lukas Podolski headed home after just 11 minutes but Shaun Maloney's free-kick before the break to hand Wigan a lifeline.
Wojciech Szczesny saved brilliantly from Arouna Kone as Roberto Martinez's side looked for a win that would keep their top flight survival hopes alive until the final weekend of the season, but three goals after the hour mark ended their Premier League existence.
Walcott guided into the corner from Cazorla's cross, Podolski doubled his tally with a chipped third and Aaron Ramsey smashed home to put the icing on a clinical Arsenal performance but confirm Wigan's place in The Championship next season alongside Queens Park Rangers, three days after claiming the FA Cup after defeating Manchester City.
Arsene Wenger's side now require a win against Newcastle United in the final game of the season to guarantee top-tier European football next season ahead of north London rivals Tottenham Hotspur, while in stark contrast Wigan must face the reality that many of their star names, including manager Roberto Martinez, could be susceptible to moves from rival clubs in the off-season.
While The Gunners were seeking to take the initiative in the race for fourth going into the final day of the season, Wigan, three days on from their FA Cup heroics were fighting for their lives at the wrong end of the table, with defeat fatal to their top flight status while a draw would leave them on the precipice.
Despite manager Martinez banning over zealous celebrations after the club won their first major trophy against City, Wigan began sluggishly and went behind after just 11 minutes as Santi Cazorla's innocuous corner bounced all the way through to allow Podolski to head home unmarked.
The hosts were pouring forward in waves, Aaron Ramsey finding the side-netting before Walcott, a scorer for Arsenal in each of their last two games, thought he's made it three on the trot but was adjudged to be offside.
Having brushed off the cobwebs, The Latics began to threaten and equalised just before the break as Maloney, was had earlier earned a soft free-kick after a coming together with Mikel Arteta, curled into the corner beyond Szczesny.
The visitors continued from where they left off after the break and Szczesny palmed away from Kone after some fine interplay with Callum McManaman on the edge of the Arsenal box.
Cazorla was presented with two opportunities to restore Arsenal's lead after Walcott's cross, Joel Robles saving brilliantly from the Spaniard to keep Wigan alive.
McManaman was withdrawn through injury following a subdued follow-up to his man-of-the-match performance in the FA Cup final, replaced by Franco di Santo on the hour mark.
However, instead of handing Wigan more attacking impetuous, the move sparked Arsenal into life and they went ahead after Cazorla broke away down the right and crossed for Walcott, who ghosted in between Antolin Alcaraz and Paul Scharner to find the corner.
And five minutes later, Athletic's Premier League lives hung by the finest of threads as Scharner played Podolski onside from Cazorla's cushioned header with the German looping the ball over the onrushing Robles.
Wigan's life-support machine was truly cut off as Ramsey broke through to rifle in from a tight angle, his first league goal for over a year, to end Dave Whelan's side's eight-year top flight existence and leave the north Londoners a win away from another sesaon of Champions League football.