The Gunners, who were knocked out in the fourth round by Jose Mourinho's Blues last season, will face the Saints at the Emirates Stadium in one of five all-Premier League ties.
Elsewhere in the draw, holders Manchester City have been handed a tie against Championship side Sheffield Wednesday, while Brendan Rodgers's Liverpool meet Middlesbrough at Anfield.
Tottenham, meanwhile, have been drawn against Nottingham Forest and Everton face a tricky trip to in-form Swansea City, who have won both their opening two Premier League games to date, including the impressive 2-1 triumph at Old Trafford on the opening day.
Another all-Premier League affair sees West Brom tackle Hull City at the Hawthorns, while Sunderland, who knocked out Birmingham City in the second round on Wednesday, host Stoke City.
MK Dons, conquerors of Manchester United on Tuesday, will host Bradford City and Fulham, relegated from England's top-flight last term, take on Doncaster Rovers at Craven Cottage.
All third round ties will take place week commencing September 22.
|THIRD ROUND DRAW IN FULL|
|West Brom||vs||Hull City|
|Leyton Orient||vs||Sheffield United|
|Manchester City||vs||Sheffield Wednesday|