If life in the top-flight had started in fairytale fashion for Ian Holloway's men, the honeymoon was rudely halted as they were trounced 6-0 at the Emirates Stadium.
The Gunners needed just 12 minutes for Walcott to set them on their way, and after Ian Evatt had been dismissed four a foul on striker Marouane Chamakh, Andrey Arshavin coolly dispatched the resulting penalty to leave the Seasiders with a mountain to climb.
Their plight deepened six minutes before the break when Walcott helped himself to a second, and the misery increased within four minutes of the restart when Abou Diaby converted Bacary Sagna's cross.
Walcott completed his hat-trick with 32 minutes of the game remaining, and Chamakh finally opened his account with seven minutes to go after passing up a series of earlier opportunities.
Gareth Bale claimed the first double of his senior career as Tottenham won 2-1 at Stoke.
The Wales international knew little about his 19th-minute opener when Ryan Shawcross's attempted clearance cannoned in off him, but there was no questioning his winner, a stunning volley from Aaron Lennon's cross on the half-hour after Ricardo Fuller had levelled.
However, the game ended in controversy with Stoke convinced a late effort had crossed the line, although not in the opinion of referee Chris Foy.
Birmingham midfielder Craig Gardner was another to strike twice as his side came from behind to beat Blackburn 2-1.
Rovers midfielder Morten Gamst Pedersen saw his 50th-minute penalty saved by Birmingham keeper Ben Foster, but then delivered the corner from which Steven N'Zonzi headed Rovers in front at St Andrews four minutes later.
However, the lead was fleeting and Gardner levelled from James McFadden's delicately volleyed cross within three minutes before smashing home a long-range winner 19 minutes from time.
Bolton striker Johan Elmander claimed a second-half brace as his side won 3-1 at West Ham.
West Ham had only themselves to blame when, having seen Carlton Cole miss a first-half penalty, Matthew Upson headed into his own net under pressure from Bolton's Kevin Davies three minutes into the second half.
Things went from bad to worse for the Hammers and they found themselves 2-0 down when Elmander powered home a 68th-minute header, and the Swede doubled his tally after Mark Noble had briefly given the home side hope by beating keeper Jussi Jaaskelainen with a second spot-kick.
Promoted West Brom bounced back from their 6-0 mauling at Chelsea last weekend with a 1-0 victory over Sunderland thanks to debutant Peter Odemwingie's first goal from the club, although they had to wait until the 81st-minute despite dominating for long periods.
Everton had to settle for a 1-1 draw at home to Wolves.
Tim Cahill fired Everton in front two minutes before the break when he smashed home the rebound from Mikel Arteta's blocked free-kick with the visitors' appealing in vain for a foul, but Sylvan Ebanks-Blake cancelled out the lead with a 74th-minute equaliser to snatch a point.