Harry Maguire, Marcus Rashford and Luke Shaw became the first Manchester United players to represent England in a major final since 1966 - but ultimately suffered anguish when Italy emerged as Euro 2020 winners on penalties.
The Azzurri triumphed 3-2 in the shootout at Wembley Stadium after the sides drew 1-1 in the initial game, during which Shaw made history by scoring the fastest ever goal in a European Championship final - clocked at just 1 minute and 57 seconds. Reds left-back Luke started the move with a pass to Harry Kane and then popped up inside the penalty area to convert a cross by Kieran Trippier, his opposite wing-back, with a clinical half-volley.
Coming on the eve of his 26th birthday, Shaw's maiden international goal had the home fans dreaming for well over an hour but Italy grew into the game as it wore on and eventually equalised through Juventus centre-back Leonardo Bonucci in the 67th minute.
Shaw fired England in front with his first international goal.
United captain Maguire had another excellent game and capped it by hammering home England's best penalty with aplomb when the contest came down to 10 nerve-shredding spot-kicks. His effort made it 2-1 after Domenico Berardi and Harry Kane both scored and Andrea Belotti's attempt was saved by Jordan Pickford.
Bonucci added to his leveller in the game with a strike in the shootout and when Rashford, who came on with Jadon Sancho in a double substitution for the last two minutes of extra-time, stepped up to the spot, he unfortunately clipped the outside of the post.
Federico Bernadeschi's goal and Gianluigi Donnarumma's save from Sancho put Italy on the brink of glory, only for Pickford to thwart Chelsea midfielder Jorginho and hand Gareth Southgate's men a last-ditch lifeline.
And so it went to the tenth pen, with Arsenal's teenage winger Bukayo Saka getting his shot on target but Donnarumma making another stop to end the Three Lions' dream of bringing football home and give the ecstatic Azzurri a second European title.
Rashford took England's third penalty in the shootout but hit the post.
Ex-United captain Roy Keane was a pundit for ITV Football and said: "It’s not a night to be critical of England, they’ve been magnificent. Instead of criticising players who miss penalties, you praise the ones who stepped up and credit to both goalkeepers, who made brilliant saves. It’s a tough night for England but sometimes you have to take your medicine and move on. The World Cup is around the corner and the players will be better for this experience."
Keane's fellow analyst and former team-mate Gary Neville added: "Every single one of them, the players, the staff, have been outstanding. But well done to Italy, they deserve it. The lads just fell short but we’re all so proud."