In arguably the biggest game of the title run-in to date, the Gunners will try to cut the gap on the table-topping Blues to one point on Saturday afternoon.
Throughout his 18-year reign, Wenger has overseen three Premier League championship wins and four FA Cup successes, and victory at Stamford Bridge would vastly improve his chances of adding to that and ending Arsenal's eight-year trophy drought.
His opposite number, though, remains unbeaten in 75 home league matches as Chelsea boss, although the Champions League quarter-finalists did suffer a 1-0 defeat to Aston Villa in their last outing.
The hosts will be without the suspended duo of one-named Brazilians Ramires and Willian, both of whom saw red at Villa Park much to the dismay of Jose Mourinho, who was also sent off by referee Chris Foy.
The Cameroonian striker, who turned 33 last week, has netted in each of his last two games and has made a habit of scoring important goals against the division's other top sides this season.
Nemanja Matic, who is ineligible for European competition, will return to fill the void left by Ramires and could be joined in midfield by both Frank Lampard and David Luiz, with Mourinho having favoured a more cautious approach against Chelsea's title rivals so far this campaign.
Injury won't deny Ashley Cole the chance to face the club he left to sign for the Blues, but Cesar Azpilicueta will. Cole is fit again following a knee problem, but will only be among the home substitutes.
Wenger heads into his landmark match without four of his most senior figures. The sidelined Aaron Ramsey, Mesut Ozil, Theo Walcott and Jack Wilshere will all miss Arsenal's game with their capital rivals.
Possible starting lineups
Chelsea: Cech; Ivanovic, Terry, Cahill, Azpilicueta; Matic, Luiz, Lampard; Hazard, Schurrle, Eto'o
Arsenal: Szczesny; Sagna, Mertesacker, Koscielny, Gibbs; Arteta, Oxlade-Chamberlain; Rosicky, Cazorla, Podolski, Giroud
Sports Mole says: 3-0