Manchester City have been handed a daunting start to the defence of their Premier League title with Pep Guardiola's team set to travel to Tottenham Hotspur on the opening day of the 2021-22 season before going on to face Arsenal, Leicester City, Chelsea and Liverpool in their first seven games.

The new campaign begins with some box-office clashes on the opening weekend (Aug. 14/15) as City travel to Tottenham and Manchester United play traditional rivals Leeds United at Old Trafford. Newly promoted Brentford start their first-ever Premier League season with a home game against London neighbours Arsenal.

Arsenal then face Champions League winners Chelsea and City before the end of August in a tough start for Mikel Arteta's team as the Gunners go into their first season without European football for 25 years.

But with the fixtures now out for the season -- they are still subject to change due to broadcasting requirements -- who will be happiest with their schedule and which teams will feel they have been given a mountain to climb? And when are the games that matter the most?

- Premier League fixtures: Man City to open vs. Spurs
- Full 2021-22 fixtures for every Premier League club
- Euro 2020 on ESPN: Stream LIVE games and replays (U.S. only)

A good start for Man United, but beware October and November

Although Manchester United's opening-day clash with Leeds is a tough one, Ole Gunnar Solskjaer's side don't face any of the so-called "Big Six" until they host Liverpool on Oct. 23. Prior to that game, United travel to Southampton, Wolverhampton Wanderers and West Ham United and play Newcastle United, Aston Villa and Everton at Old Trafford.

Having failed to win any trophy since 2017's Europa League -- with no league title since Sir Alex Ferguson retired in 2013 -- the pressure is growing on Solskjaer to win major silverware this season. And having finished as runners-up last season, United must take advantage of their favourable start this time around if they are to have any serious prospect of winning the title. A poor start would see the pressure intensify in October, when they travel to Leicester and Spurs either side of the Liverpool game. November is tough too, with games against Man City, Chelsea and Arsenal.

Tough start for City but run-in is positive

Manchester City made their worst start to a season in over 10 years last year, but they still ended up with a 12-point winning margin as champions, so their tough batch of fixtures in the opening weeks won't worry them too much. Yet City undoubtedly have a challenge in front of them in the early stages of the season, starting on the opening day at Tottenham.

Back-to-back away games at Chelsea (Sept. 25) and Liverpool (Oct. 2) will be a test for Pep Guardiola and his players, but if they can navigate their tricky start and remain in contention at the top, then their soft run-in will give them the belief they can retain the title. After facing Liverpool at the Etihad on Apr. 9, City's final six games are against Wolves, Watford, Leeds, Newcastle, West Ham and Aston Villa, so they will expect to bag plenty of points in the final weeks.

The pressure is on Arteta from day one

Arteta has to deliver at Arsenal this season having failed to secure European football last season, but the fixture computer has done the Gunners' manager no favours. An opening-day trip to Brentford could go as well as last season's 3-0 win at promoted Fulham, but the Bees are a dangerous, unpredictable team and could easily upset their illustrious neighbours.

If Arsenal slip up on day one, they will need to get something at home to Chelsea or at Manchester City in their next two games to keep the pressure off. A North London derby at home to Spurs on Sept. 25 has the potential to be very awkward for Arteta if his team fail to make a promising start to the season.

A gentle start for Liverpool, but Christmas will be a test

Jurgen Klopp's team open up with a trip to Norwich City followed by a home game against Burnley, who won at Anfield last season. A home game against Chelsea is next up, followed by a trip to Leeds, so while there is certainly an element of danger in this opening games, it is a balanced start for the 2019-20 champions.

However, the Christmas period promises to be a big test of Liverpool's prospects with three away games -- at Spurs, Leicester and Chelsea -- in the space of two weeks. Within that run of fixtures, Liverpool also face Leeds at Anfield on Dec. 26.

Demanding opening for Chelsea

Chelsea will expect to challenge for the Premier League title this season after winning the Champions League last month. But Thomas Tuchel's team, who face Europa League winners Villarreal in the UEFA Super Cup in Belfast on Aug. 11, arguably have an even tougher start than Man City.

Chelsea open up with a home game against Crystal Palace, who will be under new management following the departure of Roy Hodgson, and then face Arsenal, Liverpool, Aston Villa, Tottenham and City in their next five games. The flipside for Chelsea is that, in their final 12 league games, they only meet one fellow "Big Six" team -- a trip to Manchester United on May 15.

Tricky start for Tottenham's new boss, London derbies in September

Tottenham's new coach -- expected to be former Roma coach Paulo Fonseca -- will want a good start to their reign, but it won't be easy, especially if star striker Harry Kane gets his wish and leaves the club this summer.

But if Spurs can get a positive result against City on the opening weekend at the Tottenham Hotspur Stadium, then confidence will be high ahead of their next batch of games against Wolves, Watford and Crystal Palace. Those opening games will be crucial for the new man in charge due to the back-to-back London derbies against Chelsea and Arsenal in September. So for Spurs, there is the chance to make a really promising start to life under their new coach. But equally, if results go wrong, he will be under big pressure very early in the campaign.

THE GAMES YOU CAN'T MISS

Aug. 14: Manchester United vs. Leeds United

Last season's clash at Old Trafford ended in a 6-2 win for Solskjaer's side as both teams enjoyed an end-to-end game full of scoring chances. But while the entertainment value should be high again in this one, it is the prospect of one of the most intense rivalries in English football being played in front of fans again that makes it so appealing.

The Premier League are hopeful that stadiums will be full again at the start of the new season following almost 18 months of severe restrictions on crowd numbers due to the COVID-19 pandemic. So what better way to return to normal (or close to it, at least) than with a game between two teams backed by over 70,000 passionate supporters at Old Trafford?

Sept. 25: Arsenal vs. Tottenham Hotspur

Don't expect this fixture to matter in terms of deciding the outcome of the title race this season -- it may ultimately be nothing more than a playoff for Europa League qualification. But while both North London giants are in a period of transition, it remains a huge occasion on the fixture calendar and this early encounter will give an indication as to whether either of the teams are heading in the right direction again.

Arsenal ended last season in good form in the league, narrowly missing out on Europe after turning their results around in the second half of the campaign, so they will want to maintain that bounce under Arteta. And for Spurs, it is all about the new manager and how he starts as permanent successor to Jose Mourinho.

Sept. 25: Chelsea vs. Manchester City

The first rematch of last season's Champions League final, which Chelsea won 1-0 in Porto to claim their second European Cup. Premier League champions City will expect Chelsea to challenge for the league title this season, so Pep Guardiola will regard it as crucial that his team puts an end to their losing streak against Tuchel's side.

Chelsea have now won three successive games against City -- in the league, FA Cup and Champions League -- so a fourth win on the spin will give them a big psychological advantage over Guardiola's team. But it is the kind of test that City usually relish, so they will travel to Stamford Bridge aiming to repeat their 3-1 win at Chelsea from last January.

Oct. 2: Liverpool vs. Manchester City

This encounter between the last two Premier League champions is still THE game of the season in terms of impact on the title race.

Liverpool lost their way spectacularly last season, losing six successive home league games, but still ended the campaign in third position. Jurgen Klopp's team will expect to challenge for the title again this season and they will also be desperate to avenge last season's Anfield defeat against Guardiola's side.

In recent seasons, nobody has come close to matching Liverpool and City for consistency at the top of the Premier League and they remain the teams to beat. There will be an increased sense of motivation at Liverpool to bounce back after their dismal defence of the title last time around, so beating City will be high on their agenda.

Nov. 6: Manchester United vs. Manchester City

If Manchester United are to successfully challenge for the title this season, they simply have to win this game. United have failed to finish above City in any season since last winning the title in 2013 and the balance of power in Manchester is now firmly in the blue half of the city.

Ole Gunnar Solskjaer's side have learned how to win against their neighbours in recent seasons, but their Old Trafford record against the Blues is poor, so it is crucial that they put that right in this fixture.

Jan. 1: Chelsea vs. Liverpool

This could be an explosive start to 2022 as the two teams most likely to challenge Manchester City go head-to-head at Stamford Bridge.

By this stage of the season, we will know the shape of the title race and which teams are the favourites to finish on top. And it is set to be an intriguing battle between coaches Thomas Tuchel and Jurgen Klopp -- two Champions League winners -- as they attempt to overhaul City as champions.

Liverpool won at Chelsea in the early weeks of last season, but the Blues avenged that loss with a win at Anfield in the second half of the campaign.

Jan. 22: Chelsea vs. Tottenham Hotspur

No matter what is at stake when these two teams meet, the rivalry between both clubs ensures that it is usually eventful -- last season's 0-0 draw at Stamford Bridge was definitely a rare quiet day between Chelsea and Spurs.

Chelsea are now the top dogs in London after winning a second Champions League and, if they get their way, they could also have Kane in their team next season. Such a contentious transfer remains unlikely, but Chelsea have the money and the ambition to pull it off, and Kane wants to play for a club that wins big trophies. But even if that deal doesn't happen, Chelsea versus Spurs is always a fixture to highlight in the calendar.

March 19: Liverpool vs. Manchester United

Traditionally, this is the biggest fixture in English football -- a meeting of the two most successful and best-supported clubs in the country. But when the two sides have met at Anfield in recent seasons, it has usually turned out to be either a one-sided Liverpool victory or a dismal 0-0 draw.

United haven't won at Anfield since Wayne Rooney's goal settled a 1-0 victory in January 2016 and they haven't come close to getting a win in their recent visits. Solskjaer's side have plenty of work to do to end their miserable run at Anfield, but if they are chasing the title, they will have to get back to winning ways at Liverpool in this game.