McManaman has been rewarded for a string of impressive performances with Roberto Martinez's side, including a man-of-the-match display in Saturday's shock FA Cup final win over Manchester City.
He is part of a 23-man squad confirmed by manager Stuart Pearce on Tuesday but another wide man, Liverpool's Raheem Sterling, misses out with a thigh problem.
"I've made it my business over the last six weeks to have a real good look at Callum," Pearce, who worked with McManaman at the U20s World Cup in 2011, told the FA's official website.
"He's played so well and the culmination of that was a fantastic game in the (FA Cup) final. That will give his self-esteem the world of good.
"He came on the international scene a few years ago at U20 level and now he's found form at the right time, just before a major championship. I've seen fit to take him, even though he's not played U21 football."
With Danny Rose suspended for the Young Lions' first game against Italy in Tel Aviv on 5 June, Southampton left-back Luke Shaw is also in line for a debut, having missed February's clash with Sweden through injury.
Steven Caulker is back at Pearce's disposal after spending time with Roy Hodgson's senior squad and should reprise a formidable partnership with Craig Dawson that has not conceded a goal during a nine-game winning streak.
Wilfried Zaha, Jordan Henderson and Jonjo Shelvey are among the others in the squad with senior experience and Pearce admits he is approaching his fourth major tournament at U21 level in confident mood.
"We set out two years ago to win the tournament," he added.
"It's a four-step process; you have to get out of your group in qualification, you have to win the play-off, get out of the group in the finals, then win the tournament.
"We've done two of those, and now we want to go the rest of the way and lift the trophy."
England U21 squad:
Goalkeepers: Butland (Stoke), Steele (Middlesbrough), Rudd (Norwich)
Defenders: Caulker (Tottenham), Clyne (Southampton), Dawson (West Brom), Lees (Leeds), Rose (Sunderland, loan from Tottenham), Shaw (Southampton), Smith (Tottenham Hotspur), Wisdom (Liverpool)
Midfielders: Chalobah (Watford, loan from Chelsea), Henderson (Liverpool), Ince (Blackpool), Lansbury (Nottingham Forest), Lowe (Blackburn), McEachran (Chelsea), McManaman (Wigan Athletic), Shelvey (Liverpool), Townsend (QPR, loan from Tottenham)
Forwards: Zaha (Crystal Palace, loan from Manchester United), Marvin Sordell (Bolton), Connor Wickham (Sunderland)
England's group fixtures - live on Sky Sports (kick-off times BST):
5 June v Italy, Tel Aviv (7.30pm)
8 June v Norway, Petah Tikva (5pm)
11 June v Israel, Jerusalem (5pm)