It's all change for neighbours Manchester City too, where Manuel Pellegrini can expect a warm welcome from the home faithful as the Etihad Stadium hosts Newcastle United on the opening day.
The Chilean will do well to match the reception Jose Mourinho will receive on his second coming as Chelsea boss, with Hull City charged with the unenviable task of spoiling the Special One's special day in west London.
Cardiff City's first ever Premier League campaign kicks off with a trip to West Ham United, while Crystal Palace welcome Tottenham to Selhurst Park in an intriguing looking all-capital affair.
The Emirates will stage Arsenal's season opener as Paul Lambert's Aston Villa side travel to north London for a tough-looking start.
Mark Hughes has been handed a tough beginning to life as Stoke City boss as he takes his new side to Anfield to face Brendan Rodgers' Liverpool.
West Brom will look to build on a successful last campaign by opening up against Southampton, while Roberto Martinez begins his Everton tenure with a trip to Norwich City.
Paolo Di Canio has intimated major changes are in the offing at Sunderland so it will likely be a new look Black Cats side that begin their campaign with a home game against Fulham.
All opening fixtures will played on the weekend of August 17-19.
Hull's fans will relish their festive programme, with Manchester United heading to the KC Stadium on Boxing Day, while Manchester City against Liverpool is another tasty-looking December 26 encounter.
The season wraps up on May 11, with three of the expected title chasers finishing on the road. Chelsea head to Cardiff, Manchester United go to Southampton and Arsenal are at Norwich, with Manchester City at home to West Ham.
In the Championship, Harry Redknapp's rebuilding mission at QPR will start on August 3 when Sheffield Wednesday visit Loftus Road on the first day of the new season.
Rangers are spending the summer licking their wounds after their high-profile relegation from the Premier League, and Redknapp has warned his big-name players they need to be ready for the second-tier's 46-game slog.
That will begin against Dave Jones' Wednesday, followed by a trip to Huddersfield a week later and then a home meeting with Ipswich.
Owen Coyle's first game in charge of Wigan will take him to Oakwell for a meeting with Barnsley. Coyle took the job this week after Roberto Martinez left the relegated FA Cup winners for Everton.
The other side to have dropped into the Championship, Reading, host Ipswich, with manager Nigel Adkins set to try and win a fifth promotion.
Play-off final losers Watford - who will be be adapting to the new overseas loan rule - start at Birmingham, while defeated semi-finalists Brighton and Leicester are away to Leeds and Middlesbrough respectively.
The Championship, League 1 and League 2 seasons all culminate on Saturday May 3.
League 1 champions Doncaster kick off their second-tier return at home to Paul Ince's Blackpool, runners-up Bournemouth are at home to Charlton and play-off winners Yeovil head to Millwall for Steve Lomas' first game in charge.
The remaining opening-day games feature two of the Football League's 125th anniversary games - Burnley at home to Bolton and Blackburn at Derby - plus Nottingham Forest's hosting of Huddersfield.