Fans will get their first glimpse of how one of the contenders will fare when Arsenal, fresh from their Community Shield victory over Chelsea, face Leicester in the season opener at the Emirates Stadium.
Arsene Wenger brokered a fragile truce with Arsenal's dissenting fans by winning the FA Cup last season, but the Gunners boss has no margin for error after going 13 years without Premier League glory.
Last season was by far the most difficult of Wenger's 21-year reign, with Arsenal's on-pitch travails exposing him to furious protests from angry fans.
Having ended months of speculation by signing a new two-year contract, Wenger believes if his players put on a united front, the exasperated fans will fall into line behind them.
"A lot of the trouble was created by my own situation. Maybe I made a mistake," said Wenger, who will be without want-away Chile star Alexis Sanchez against Leicester due to injury.
"Overall I believe that it's down to us. The trend has always to come from the team."
The bulk of the opening weekend's fixtures will be played on Saturday and Sunday, with Chelsea starting at home to Burnley.
City travel to new-boys Brighton, back in the top tier after a 34-year absence, while United host West Ham.
Liverpool, trying to fend off Barcelona's interest in £100 million-rated forward Philippe Coutinho, are at Watford.
Despite finishing second last season, Tottenham, who face promoted Newcastle on Sunday, have boldly abstained from the spending and are yet to make a single signing.
The merits of that cautious approach should become clear throughout a fascinating season that serves as a referendum on the go for broke era.
Fixtures (1400 GMT unless stated):
Arsenal v Leicester (1845 GMT)
Brighton v Manchester City (1630 GMT), Chelsea v Burnley, Crystal Palace v Huddersfield, Everton v Stoke, Southampton v Swansea, Watford v Liverpool (1130 GMT), West Brom v Bournemouth
Manchester United v West Ham (1500 GMT), Newcastle v Tottenham (1230 GMT)