The 22-year-old forward was called up when Wigan star McManaman had to withdraw after being ruled out for three months with an ankle injury he suffered in Tuesday's 4-1 Premier League defeat at Arsenal.
Delfouneso, who has scored four goals in 16 outings for the Under-21s and was in the squad for Euro 2011 in Denmark, was the natural replacement in coach Stuart Pearce's opinion.
Pearce said: "Nathan was very unfortunate not to make the squad in the first place. He has contributed a great deal to the Under-21s in qualification and he was unlucky that Callum McManaman's form was such that he had forced his way into the reckoning late on."
England's tournament starts against Italy in Tel Aviv on June 5.