Premier League champions Manchester City will open the defence of their trophy away to Tottenham.
City are among the clubs linked with a move for Spurs striker Harry Kane, throwing up the prospect of the England captain lining up against the Londoners on the opening weekend of the 2021/22 season on August 14.
Pep Guardiola's City cruised to the Premier League title by 12 points last season ahead of Manchester United, who open their campaign against Leeds United at Old Trafford after the new fixtures were released on Wednesday.
Also on the first weekend, Champions League winners Chelsea will host Crystal Palace, newly promoted Brentford are at home to Arsenal, while Jurgen Klopp's Liverpool travel to Norwich City, who won the Championship last season.
Everton, still to recruit a new coach after Carlo Ancelotti left for Real Madrid, are home to Southampton, with FA Cup holders Leicester City playing Wolves at the King Power Stadium.
Watford, the third promoted side, take on Aston Villa at Vicarage Road, Brighton visit Burnley and West Ham are away to Newcastle United in the other first weekend fixtures.
The Premier League campaign ends on May 22 with Manchester City, Liverpool and Chelsea all finishing at home against Villa, Wolves and Watford respectively, while Manchester United round off their campaign at Crystal Palace.
There are a number of early meetings between the big six, who were all involved in the aborted Super League fiasco, with the weekend of September 25 seeing a repeat of the Champions League final when Manchester City travel to Chelsea.
All fixtures are subject to change for TV coverage. Currently there are only four rounds of midweek fixtures, with three of them in December.