Wenger described the result as "one of the worst days" of his career and his misery was compounded by handsome victories for Liverpool and Manchester City that saw his side slump to fourth place in the table.
Luis Suarez scored a hat-trick as Liverpool won 6-3 at Cardiff City to move to within four points of Chelsea, while City are two points further back -- but with three games in hand -- after Yaya Toure also claimed a treble in a 5-0 win over Fulham.
Meanwhile, Manchester United striker Wayne Rooney scored an astonishing 58-yard lob in a 2-0 win at West Ham United.
Arsenal are now seven points below Chelsea, albeit with a game in hand, after Wenger's side were blown away by a flurry of first-half goals from Samuel Eto'o, Andre Schurrle, Eden Hazard and Oscar at Stamford Bridge.
Hazard's goal came from the penalty spot after Arsenal midfielder Alex Oxlade-Chamberlain had handled the ball on the line, but a peculiar case of mistaken identity meant that his team-mate Kieran Gibbs was sent off instead by referee Andre Marriner.
Oscar claimed his second goal in the 66th minute before substitute Mohamed Salah scored to seal the club's biggest ever win over Arsenal and give manager Jose Mourinho his most emphatic Chelsea success.
"This defeat is my fault. I take full responsibility for it," said a crestfallen Wenger, who then chose not to attend his post-match press conference.
"I don't think there's too much need to talk about the mistakes we made. We got a good hiding today."
Mourinho, whose side had crashed to a 1-0 defeat at Aston Villa last weekend, said: "At 2-0 after seven minutes, the game is over. We were too strong.
"We had momentum, but it stopped last Saturday against Aston Villa for some reason. Now we are trying to build more momentum."
Chelsea remain top, but Liverpool are hot on their heels, and have a game in hand, after twice coming from behind to overwhelm second-bottom Cardiff in south Wales.
Ole Gunnar Solskjaer's side threatened to pull off an upset by going ahead through Jordon Mutch in the ninth minute and then retaking the lead through Fraizer Campbell after Suarez had equalised.
Centre-back Martin Skrtel equalised in the 41st minute, however, and Suarez's two second-half strikes, allied to goals from Skrtel and Daniel Sturridge, secured a sixth successive victory for Liverpool, with Mutch replying for Cardiff.
- Suarez closes on record -
Suarez now has 28 league goals for the season, just three short of the record for a 38-game campaign.
"He is a remarkable player," said Liverpool manager Brendan Rodgers.
"His determination, his desire, his will is at such a big level. He is a world-class player who is enjoying his football, and long may it continue."
City moved above Arsenal into third place after Toure's treble helped to put paid to bottom club Fulham, who had defender Fernando Amorebieta sent off early in the second period.
Toure's first two goals came from the penalty spot and he completed his first City hat-trick with an effortless 25-yard curler before Fernandinho and Martin Demichelis added late efforts of their own.
"It is important because maybe the last month we have not been scoring so many goals," said City manager Manuel Pellegrini.
"But we're always creating chances so in that sense I was very quiet and not worried about that. I hope we continue."
Rooney muscled in on the headlines later in the day, scoring twice at Upton Park as his side built on the momentum of their mid-week Champions League victory over Olympiakos with victory at West Ham.
The England striker opened the deadlock in the eighth minute with an extraordinary goal, spotting West Ham goalkeeper Adrian off his line and lifting the ball over him from just inside the hosts' half.
He then claimed a fortuitous second goal in the 33rd minute when an attempted clearance by Mark Noble struck him and cannoned into the net.
It was his 212nd goal in United's colours, taking him above Jack Rowley into third place on the list of the club's all-time leading scorers.
Norwich City were the only team in the bottom seven not to lose on Saturday, winning 2-0 at home to Sunderland through goals from Robert Snodgrass and Alexander Tettey to climb seven points clear of the bottom three.