Sunday's third-round draw pitted the Champions League winners against Nigel Adkins' Saints over the weekend of January 5 and 6, and both club and manager will be hoping the headlines surrounding them are happier ones by then.
Benitez has endured a miserable first 11 days in the job since replacing Roberto Di Matteo last month, with a number of fans voicing their opposition to his appointment and only two points taken from the first nine on offer as the Blues slumped to a 3-1 loss at West Ham on Saturday.
The Spaniard has FA Cup pedigree though, having won it with Liverpool in 2006, while Chelsea will be starting their defence of a trophy they have won four out of the last six seasons.
They have not faced Southampton yet this season - the clubs were due to meet on December 15 but Chelsea will be in Japan taking part in the World Club Cup.
Perhaps the most attractive all-Premier League tie comes at Upton Park, though, where West Ham will meet 11-time winners Manchester United.
The two met in the league just four days ago, the Red Devils winning 1-0, but the two have enjoyed many memorable duels over the years, particularly when Paolo Di Canio scored the only goal to knock Sir Alex Ferguson's men out in 2001.
The draw also threw up a repeat of the 1987 final between Tottenham and Coventry.
The Sky Blues famously beat Spurs 3-2 after extra-time at the old Wembley, a win which included a stunning Keith Houchen diving header.
Newcastle have the chance to avenge last season's loss to Brighton, Aston Villa are at home to Ipswich and Manchester City take on Watford, but Liverpool may not be relishing their tie.
Brendan Rodgers' men must head to Lincoln or Mansfield, both Conference sides, who drew 3-3 on Saturday.
"It sounds fantastic," Lincoln manager David Holdsworth told Sky Sports News.
"The prospect to get through and face Brendan's men is a daunting one, but one we would embrace and it would be a wonderful occasion for each set of supporters.
"The draw has been made now, it's a fact, and we have to deal with it and try and get through."
Arsenal's last trophy was the 2005 FA Cup, but the first stop in their quest to win it again will be Swansea's Liberty Stadium, the side who beat them 2-0 at the Emirates Stadium in the league on Saturday.
The 2011 runners-up, Stoke, go to Championship high-flyers Crystal Palace, while the lowest-ranked side left, Hastings, will face a long journey to Middlesbrough if they beat Harrogate Town in a replay.
Sean Ray, manager of the Isthmian League side, told Sky Sports News: "It's a real dream come true. The dream carries on. The boys are buzzing and are right up for it. It would be an unbelievable tie.
"We took over 300 fans to Harrogate and would take more than 500 to Middlesbrough."
Premier League Wigan will be at home to Bournemouth, with fellow top-flight sides Sunderland and Norwich at Championship sides Bolton and Peterborough respectively.
The 1975 runners-up Fulham host Blackpool, nearly 60 years on from their involvement in the Matthews Final, while QPR, bottom of the Premier League, face West Brom.
Reading go to Crawley, whose director of football is the Royals' former boss Steve Coppell, while Everton will head to the winner of Monday's tie between Cheltenham and Hereford.
In three all-Championship ties, Charlton host Huddersfield, Barnsley take on Burnley at Oakwell and Leeds and Birmingham meet up at Elland Road, while MK Dons go to Sheffield Wednesday after winning their grudge match with AFC Wimbledon.
Leicester are at home to Burton, Derby play Tranmere, Nottingham Forest take on Oldham and Millwall meet Preston.
Aldershot take on Rotherham or Notts County, Accrington and Oxford replay for the right to play Sheffield United, while Bury or Southend will face Bradford or Brentford.
Wolves go to Kenilworth Road to play Luton, Blackburn tackle Bristol City and Barrow or Macclesfield, whose game was frozen off, know a meeting with Cardiff awaits.
Steve Bruce, a winner with Manchester United as a player, must prepare his Hull side for a clash with Leyton Orient after they beat Alfreton 4-2 on Sunday afternoon.
FA Cup third-round draw
Crystal Palace vs Stoke
Brighton vs Newcastle
Tottenham vs Coventry
Wigan vs Bournemouth
Fulham vs Blackpool
Aston Villa vs Ipswich
Charlton vs Huddersfield
Barrow/Macclesfield vs Cardiff
Barnsley vs Burnley
Manchester City vs Watford
Swansea vs Arsenal
Leicester vs Burton
Millwall vs Preston
Cheltenham/Hereford vs Everton
Derby vs Tranmere
Crawley vs Reading
Aldershot vs Rotherham/Notts County
Middlesbrough vs Harrogate/Hastings
Accrington/Oxford vs Sheffield United
Southampton vs Chelsea
QPR vs West Brom
Peterborough vs Norwich
Lincoln/Mansfield vs Liverpool
Bolton vs Sunderland
Nottingham Forest vs Oldham
West Ham vs Manchester United
Hull vs Leyton Orient
Blackburn vs Bristol City
Leeds vs Birmingham
Bury/Southend vs Bradford/Brentford
Luton vs Wolves
Sheffield Wednesday vs MK Dons
Ties will be played on the weekend of January 5 and 6.