Defoe stunner ensures England see off Italy
Substitute Defoe, netting for the 16th time in 49 internationals, capped a rapid counter-attack 11 minutes from time when he curled in from just outside the penalty area.
It was England's first victory over Italy since 1997 and came little over seven weeks since Cesare Prandelli's side beat England 4-2 on spot-kicks in Kiev after a goalless 120 minutes.
Both sides were unrecognisable from that June 24 meeting, fielding young and experimental sides before the serious business of 2014 World Cup qualifying starts next month.
Captain Daniele De Rossi headed Italy in front after 15 minutes when he met an inswinging corner from Alessandro Diamanti and powerfully headed past debutant goalkeeper Jack Butland into the roof of the net.
Butland, 19, became the youngest keeper to play for England despite never having played in the country's top two divisions.
England hit back 12 minutes later from another set piece, defender Phil Jagielka ignoring the attentions of Federico Balzaretti to stoop to head in Frank Lampard's corner for his first international goal.
"It was great to be able to give some of the senior players a rest and to be able to blood some new players, some fresh talent and they answered the challenge in the best possible way with a great victory," England manager Roy Hodgson told ITV.
"I don't think there was a great difference between what we did in the Euros and what we did tonight. Perhaps we just played with that little bit more composure."
As well as Butland, Hodgson blooded midfielder Tom Cleverley and handed debuts after the break to keeper John Ruddy, defender Ryan Bertrand and midfielder Jake Livermore. Midfielder Michael Carrick also made his first international start since 2010.
Italy, beaten by Spain in the final of Euro 2012, handed debuts to strikers Stephan El Shaarawy and Mattia Destro, the latter wasting his own good control from a long ball midway through the first half when he blasted wastefully wide from a good position.
Ruddy, who replaced Butland at half-time, saved well at his near post from Destro and then substitute and fellow debutant Federico Peluso spurned a good chance by shooting wide.
Peluso was almost left red-faced at the other end from James Milner's dangerous cross but flailing keeper Salvatore Sirigu prevented an own goal.
Bertrand had an immediate impact when he was in the right place on the goal-line to clear and from the breakaway England struck.
James Milner led the counter-attack and his swift pass found Defoe on the edge of the box. With his back to Ignazio Abate, the striker swivelled and rifled in a fierce shot that thundered past Sirigu.