And the Gunners remained at the summit when previous leaders Liverpool failed to beat title favourites Manchester City, who claimed a hard-fought 2-1 victory at the Etihad Stadium in the late game.
Walcott's two goals in Arsenal's 6-3 thrashing at Manchester City on December 14 had no effect on the result but at least announced his return to form as well as fitness after abdominal trouble.
But at Upton Park his impact turned the game on its head, after the hosts stole a 1-0 second-half lead through striker Carlton Cole.
Cole prodded home after goalkeeper Wojciech Szczesny failed to hold a straightforward shot on goal.
Arsenal hit back through Walcott though, who scored twice in three minutes to take his season's goal tally to five.
Lukas Podolski marked his return with a goal too, with Olivier Giroud claiming an assist.
Manchester City's victory ensured they retained their imperious 100 per cent home record as Manuel Pellegrini's side made it an impressive nine out of nine - with 37 goals scored - to move into second place, a point behind Arsenal.
However, had Raheem Sterling's effort not been wrongly ruled out for offside before either side had scored - and goalkeeper Simon Mignolet not made a hash of Alvaro Negredo's winner - Brendan Rodgers' side could well have got much more out of this game.
As it was they contributed much to an enthralling match which was billed as a test of their title credentials.
Philippe Coutinho's opener sparked the home side into life and after Vincent Kompany had equalised from a corner, Negredo's 14th goal of the season ultimately clinched another three points.
Liverpool drop to fourth as a result of the defeat, but are just three points behind the Gunners.
Jose Mourinho kept his promise to mix up selection by restoring Ashley Cole at left-back and the England defender promptly repaid that call by laying on the pass that allowed Eden Hazard to score the decisive goal.
The American stopper struggled to deal with Leon Osman's undersold back-pass, and paid the price when he tripped Black Cats midfielder Ki Sung-yueng.
Ki netted the resulting penalty, with Joel Robles unable to stop Sunderland taking the lead after replacing Osman.
And the visitors held out to grind to victory.
Christian Eriksen's free-kick put the home side ahead but Spurs were pegged back by Jonas Olsson's goal after 38 minutes.
Spurs pushed and pushed after the break but could not find a winner, with the match ending in a draw.
Mauricio Pochettino's Southampton swatted Mackay's men aside in Wales, top-scorer Rodriguez making the early inroads before Lambert completed a 3-0 drubbing.
Cardiff's fans started the day with a pre-match march against Vincent Tan, at the end of a week where the owner had relented from his decision to sack boss Mackay.
But the home fans left dejected, with Mackay staring down more scrutiny from owner Tan, after Southampton dominated and claimed deserved victory.
Remy's double and Yoan Gouffran's eighth league goal of the season helped the Magpies build on last weekend's 3-0 victory at Crystal Palace.
Yohan Cabaye notched a fourth from Mathieu Debuchy's assist, while Papiss Cisse scored his first goal in 10 games as the tie wound up a complete mismatch.
Stoke had Glenn Whelan and Marc Wilson sent off in a frenetic first half, and those dismissals ultimately turned the game in Newcastle's favour.
The visitors took the lead when Oussama Assaidi slotted home, but Whelan picked up two yellow cards in the space of six minutes for Stoke's first dismissal.
Then Wilson produced a professional foul on Remy for his early bath, only for Remy to miss the resulting spot-kick.
Only moments later Frenchman Remy atoned for that miss, putting Newcastle back on level terms.
And after the break Alan Pardew's men were able to dismantle their denuded opponents.
The former Peterborough striker's brilliant last-minute effort secured a 1-0 win for Tony Pulis' side at the end of a gritty Villa Park contest.
Rene Meulensteen's men came from behind to claim 2-1 victory at Carrow Road and leapfrog West Ham as they moved out of the relegation zone.
Gary Hooper's seventh league goal of the season and fourth in successive home games handed Norwich a 1-0 lead after 13 minutes.
But Pajtim Kasami placed a free-kick into the bottom right of the Norwich goal to bring Fulham back on terms just past the half-hour mark, leaving the scores locked at 1-1 at half-time.
It had been a dream start but a nightmare finish for Hull City defender James Chester in the day's lunchtime kick-off, as he scored for both teams in the Tigers' agonising 3-2 defeat to his former club Manchester United.
Chester and David Meyler handed Steve Bruce's side a 2-0 lead after just 13 minutes at the KC Stadium.
But if manager Steve Bruce, also a former United defender, started to sniff a first ever victory over his old club, any such thoughts vanished thanks to quickfire goals from Chris Smalling and Wayne Rooney.
Rooney's 150th Premier League goal for United levelled the game before the half-hour mark and the scores stayed locked until midway through the second half, when Chester put through his own net under pressure from Rooney.
United held out for the victory, their third consecutive league triumph, despite Antonio Valencia's late dismissal.