But just when it appeared as if the match was petering out to a draw, Defoe finished off a counter-attack led by fellow substitute James Milner, sending a 20-yard shot arrowing into Salvatore Sirigu's top-left corner.
The victory may not make up for the pain of June's EURO 2012 quarter-final defeat on penalties to the same opponents, but it was their first win against Gli Azzurri since a 2-0 friendly triumph in Nantes, France, in June 1997.
"It was a spectacular goal, and a great way to win the game," said Hodgson. "It's something none of us who have watched him play for Tottenham over the years, and have seen the quality he has, are surprised about."
Just 52 days had passed since these nations met in Kiev, but the circumstances were entirely different. England and Italy took to the field with experimental sides, the focus firmly on the upcoming 2014 FIFA World Cup™ qualifying campaign.
Both coaches opted to hand chances to fringe players and young talent, with 19-year-old Jack Butland becoming England's youngest goalkeeper in 124 years. He was rarely called upon in his 45 minutes on the field before he made way for Norwich City's John Ruddy, another novice.
But while a half-empty Wankdorf Stadium in Bern felt a million miles away from the tension of that night in Kiev on 24 June, the pattern of the game was familiar early on.
Italy may have needed penalties to win that quarter-final, but Cesare Prandelli's side were far superior technically, and they appeared so again even without master creator Andrea Pirlo.
That said, the goal that gave them the lead after 15 minutes had something of an English stamp on it - after Butland had turned a deflected Alessandro Diamanti free-kick around the post, the former West Ham United player swung in a corner that De Rossi headed into the roof of the net.
Proceedings livened up after that, with Adam Johnson forcing a good save from Sirigu before the debutant Mattia Destro shot over following a superb Alberto Aquilani pass over the top.
But then England equalised with a goal almost identical to that scored at the other end, with Jagielka heading in following a Frank Lampard right-wing corner.
England appeared galvanised after that, and Lampard in particular. The Chelsea man, who missed EURO 2012 due to a thigh injury, spoke on the eve of the game how he felt fresher than ever after a five-week long break.
And he came mighty close to putting Hodgson's men ahead twice before the interval, first with a shot that was well saved by Sirigu, and then with a 20-yard free-kick that landed on the roof of the net.
As is often the case with August friendly internationals, an enjoyable first half gave way to a second period frequently interrupted by substitutions from both sides.
One of those, Ruddy, made a good stop low to his right to save from the lively Destro, while another, Joleon Lescott, hit the woodwork from barely a yard out at the other end before Defoe's strike settled it.