The victory gives Chelsea 69 points for a seven-point cushion over Arsenal and Liverpool, who face Cardiff City later on Saturday. Manchester City, fourth on 60 points, are playing league doormats Fulham.
The Man of the Match, however, was referee Andre Marriner, who was left red-faced after he sent off the wrong Arsenal player just 15 minutes into the contest.
Arsenal were already trailing 2-0 on goals from Samuel Eto'o and Andre Schuerrle when Marriner gave a penalty and a red card to Kieran Gibbs after teammate Alex Oxlade-Chamberlain handled a shot from Eden Hazard on the goalline.
Replays showed Oxlade-Chamberlain clearly mouthing "it was me" to Marriner in the aftermath but the referee stuck by his original decision.
Eden Hazard converted the penalty and Oscar added a fourth to put Chelsea 4-0 up at halftime. Oscar tallied again in the 66th minute to make it 5-0. Egyptian forward Mohamed Salah added the sixth goal on 76 minutes.
The result was a bitter disappointment for Wenger. When he took the helm of the club 1,000 matches ago in 1996, Arsenal called Highbury home, were yet to qualify for the UEFA Champions League and Ian Wright was leading the line.
Wenger has since gone on to win three Premier League titles, qualify for 15 consecutive UEFA Champions League tournaments and lift four FA Cups.
"I can't believe it is such a long time. Why? Because you're always focused on looking forward to the next game and when you look back you think I made quite a distance there," he said before the match.
"Despite that, your only interest is the next game, our drug is the next game, the hope for the next game, the desire to win the next one."