England's quest to end 55 years of hurt without winning a major tournament starts in Group D with the chance to gain revenge on Croatia for World Cup heartbreak and a much-anticipated clash with neighbours Scotland.
AFP Sport casts its eye over the four teams trying to reach the knockout stage.
Rarely has an England manager been so spoiled for talent than Gareth Southgate with the squad he has at his disposal.
Captain Harry Kane will be aiming for another Golden Boot after finishing top scorer at the 2018 World Cup and the Premier League this season, but will ably assisted by the likes of Jadon Sancho, Phil Foden, Jack Grealish, Marcus Rashford, Raheem Sterling and Mason Mount.
England will also have home advantage for all three group games at Wembley and could play their last 16 tie, semi-final and final at home if they progress that far.
Central defence is the one area where Southgate is not blessed with a wealth of options and an ankle ligament injury to Harry Maguire could prove costly if the Manchester United captain is not fit to partner John Stones at the back.
Southgate was praised for an unexpected run to the semi-finals at the World Cup three years ago, but the demands are far higher this time round.
At just 21, Foden already has three Premier League titles to his name at Manchester City. This season was his breakthrough into being one of Pep Guardiola's most important players at club level, taking his international teammate Sterling's place for the biggest games.
A disciplinary incident when he was sent home from breaking coronavirus rules in Iceland while on international duty for a Nations League game has so far disrupted his international career, but there is a clamour for Southgate to start Foden in the game against Croatia on June 13.
Scotland have made it to a first international tournament in 23 years the hard way, winning penalty shootouts in Nations League playoffs against Israel and Serbia.
Despite a difficult draw, there is a quiet confidence that a side boasting a strong core of proven Premier League performers in Andy Robertson, Kieran Tierney, John McGinn, Scott McTominay and Stuart Armstrong could pull off a surprise by making it through the group stage for the first time ever.
Much will depend on the home games against the Czech Republic and Croatia with the backing of 12,000 fans at a Hampden reduced from capacity because of Covid-19 restrictions.
In the absence of a proven international striker, McGinn has become Clarke's most reliable source of goals with nine goals in his last 14 appearances for his country.
The 2018 World Cup finalists are without some of the key figures from their heroics in Russia with Ivan Rakitic and Mario Mandzukic now retired from international football.
At 35, Luka Modric remains vital to his nation's fortunes but there will be concerns over how much the playmaker has left in the tank after 48 games for Real Madrid this season.
Two disappointing Nations League campaigns have sparked fears this is a Croatia team in transition, but they often save their best for the big occasion on the international stage.
Modric won the Ballon d'Or on the back of his performances in Russia three years ago and his country need him to hit those heights again if he is to carry a less talented squad into the latter stages.
Despite his advancing years, Modric was rewarded with a new contract at the Bernabeu last month after a season in which he showed no sign of his age.
The Czechs inflicted England's first defeat in a qualifier for 10 years in October 2019 and are a force to be reckoned with again under Jaroslav Silhavy.
West Ham duo Tomas Soucek and Vladimir Coufal have shone in the Premier League this season, while a core of the Slavia Prague side that reached the Europa League quarter-finals form the backbone of the side.
Soucek scored 10 goals in his first full season with the Hammers to become one of the most potent threats in the Premier League from midfield. At 6ft 4in (1.92m) he is a constant threat from set-pieces and scored a hat-trick in a recent World Cup qualifier against Estonia.