England will take on Belgium, Denmark and Iceland in the Uefa Nations League.
The Three Lions faced Roberto Martinez's Belgium side twice at the 2018 World Cup, once at the end of the group phase and again in the third-place play-off, losing on both occasions.
They are due to face the Danes in a friendly later this month - coronavirus permitting - while they famously lost to Iceland in Nice at Euro 2016.
Wales and the Republic of Ireland will meet again after they were drawn in the same group.
Ryan Giggs' men will take on the Irish in Group Four of League B in Uefa's competition, which was a big success in its inaugural edition in 2018-19.
The sides met in that first competition too, with Wales winning both encounters.
The other sides in Group B4 are first-time Euro finalists Finland and Bulgaria.
Scotland, who are due to take on Israel in a Euro 2020 qualification play-off later this month, will also face them in the 2020-21 Nations League.
Steve Clarke's men will also face the Czech Republic and Slovakia in Group B2.
Northern Ireland were drawn in Group B1 alongside Austria, Norway and Romania.
France and Croatia, who met in the 2018 World Cup final, were paired together in Group A3, while Spain and Germany go head-to-head in A4.
The group matches will be played between September and November this year.
The group winners from League A will contest the Nations League finals in June 2021, with one of them being selected to host it.
The competition also provides a back door to qualification for the 2022 World Cup.
The two highest-ranked Nations League group winners who do not either win their World Cup qualifying group or finish as runners-up will enter a 12-team play-off to secure the final three European places at the finals in Qatar.
England boss Gareth Southgate is relishing the test posed by some new opponents.
He said: "There are some good matches.
"It's nice to play some different teams in competitive games. We've obviously had quite a few games with Croatia recently and with Switzerland.
"All of the groups are quite tough and a really good fixture with Belgium as well - a team we haven't played as much in the last couple of years."
The England boss believes the higher calibre of matches will help him assess where his side are.
"We could have got tougher with the pot with Germany and Croatia in that fourth pot of seeds. But that's the Nations League," he added.
"We found it a really good competition last time and that was the excitement it brought us playing those top matches rather than having friendlies, which are important for us this month in terms of preparations for the finals but in that September, October, November period the competitive games are much better."
Southgate hopes England have developed another facet of their game in the competition.
He said: "The best way to improve is to play the best teams.
"We got very proficient in the European qualifiers at beating teams who defended deep and managed to score a lot of goals, but you are only developing one part of your game in those tests.
"These matches will be a greater test of our all-round game than those and obviously it will also be on the back of a summer that we don't know the outcome and where we will be as a team either (after the Euro 2020 finals), but we also blooded some really good young players through the competition last time."