Wenger was hoping to celebrate his milestone by cutting Chelsea's lead to a point, but instead his side were blown away by a flurry of first-half goals from Samuel Eto'o, Andre Schurrle, Eden Hazard and Oscar.
Hazard's goal came from the penalty spot after Arsenal midfielder Alex Oxlade-Chamberlain had handled the ball on the line, but a bizarre case of mistaken identity meant that his team-mate Kieran Gibbs was sent off instead.
Oscar completed his brace 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.
Arsenal retain a game in hand on Chelsea and have the consolation of an FA Cup semi-final to look forward to, but they are now at risk of being left behind in the title race. (Suggested read: Wenger takes blame for 'one of worst days' for Arsenal F.C.)
Liverpool can move to within four points of Chelsea with victory at second-bottom Cardiff City later on Saturday, while fourth-place Manchester City will climb above Arsenal, with two games in hand, if they beat bottom club Fulham.
Arsenal were the first team to threaten at a sun-soaked Stamford Bridge, with Olivier Giroud forcing Petr Cech to make a smart save in the fourth minute, but from then on it was one-way traffic.
Eto'o opened the scoring a minute later, cutting inside Oxlade-Chamberlain and curling home, before Schurrle made it 2-0 two minutes later with a drilled shot into the bottom-left corner.
Eto'o was then forced off due to an apparent hamstring injury, with Fernando Torres entering the fray, but Chelsea continued to attack.
- 'Ref, it was me!' -
The 15th minute witnessed the game's most peculiar incident, as a diving Oxlade-Chamberlain used his left hand to block a shot from Hazard that was drifting narrowly wide of the Arsenal goal.
Referee Andre Marriner pointed to the spot, but sent off Gibbs, rather than Oxlade-Chamberlain, who could be seen on television vainly telling the official: "Ref, it was me!" (Read full report here)
Hazard coolly lifted his spot-kick down the centre of the goal and there was even more misery to come for Wenger before half-time as Oscar tapped in Torres's low cross to further swell Chelsea's lead.
It was the second time this season that Arsenal had gone 4-0 down in the first half, after their 5-1 loss at Liverpool last month, and the second period brought yet more misery for Wenger's beleaguered side.
Oscar beat goalkeeper Wojciech Szczesny with a shot from outside the box before Salah ran through and slotted home his first goal since his January move from Basel.
Elsewhere on Saturday, seventh-place Manchester United will hope to harness the momentum from their 3-0 victory over Olympiakos in the Champions League in mid-week when they visit West Ham United.
Third-from-bottom Sunderland visit Norwich City and fourth-bottom Crystal Palace travel to Newcastle United, while Hull City host West Bromwich Albion and Everton tackle Swansea City at Goodison Park.