Chelsea, Arsenal and Tottenham will tackle each other as part of pre-season preparations to help support better mental health in The Mind Series during August.
The London rivals are set for three fixtures ahead of the new Premier League 2021-22 campaign.
Arsenal will host European champions Chelsea on August 1, with Spurs heading to Stamford Bridge three days later before a showdown between the two north London clubs at Tottenham Hotspur Stadium on August 8.
Funds raised from the series will be split between Mind, the UK's leading mental health charity, and the respective club foundations, which each deliver projects to support mental health and wellbeing in communities both at home and overseas.
Chelsea boss Thomas Tuchel said on the club website: "I am pleased that my first pre-season with Chelsea contains such high-level fixtures against such top-quality opponents. Hopefully there can be plenty of fans in the stadiums.
"Derby matches against Arsenal and Tottenham cannot fail to have a competitive edge, which is what the team needs as we prepare for the season, and knowing the games will benefit charities as important as Mind and our own foundation adds much value to the series."
As part of the campaign, £5 from each ticket sold will support charitable projects, with 25 per cent going to Mind.
Gunners boss Mikel Arteta also welcomed his club's involvement.
"As we take steps forward out of the pandemic, we're happy to play in a series which promotes better mental health," said the Arsenal manager, who tested positive for Covid-19 during March 2020 which resulted in the Premier League deciding to suspend all matches.
"The last 18 months have been incredibly difficult and so many people – including many of our own fans – understandably need some extra support for their mental wellbeing.
"Of course, these pre-season games will provide our teams with excellent high-quality preparation ahead of next season.
"But also very importantly they will be raising funds and awareness for organisations, like Mind, who give their outstanding support to those who need it the most in difficult circumstances."
Tottenham are still to appoint a new manager, and it remains to be seen whether one will be made ahead of the Mind Series against their local rivals.
"We expect the matches to be fiercely competitive London derbies that will get the fans excited for the season ahead, whilst providing perfect preparation for the players," said Tottenham managing director Fabio Paratici.
"The interest this will create will in turn provide a huge and much-needed boost to Mind – a charity that has such a vital role to play in the lives of so many following the difficult times we have all experienced – as well as our own foundations."
Mind chief executive Paul Farmer hopes the high-profile fixtures can help extend the charity's reach.
"We know from our work in the sector that football has the power to create real change, not least around mental health," he said.
"The platform that these three huge clubs can provide us with will allow us to get our message out to thousands more people that they have somewhere to turn when they need support."