The Aston Villa forward, who has scored four goals in 16 outings for Stuart Pearce's side, comes in to the 23-man party after Wigan winger McManaman was ruled out with an ankle injury.
The 22-year-old featured in both Under-21 matches in March, scoring in the 3-0 victory over Romania at Wycombe.
Delfouneso was also in Pearce's squad for Euro 2011 in Denmark, while two years earlier he was a valuable member of the U19s side that reached the European Championship Final, finishing the tournament with the golden boot.
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 will kick-off this year's finals against Italy in Tel Aviv on 5 June.