Cassano put Italy ahead in the eighth minute with a splendid volley following a long pass from Daniele De Rossi, then doubled the lead with a well-placed low shot from the edge of the area in the 53rd.
Northern Ireland defender Gareth McAuley then scored an own goal in the 74th by redirecting a pass from Federico Balzaretti.
Italy, which had already qualified for next year's tournament, finished with 26 points atop Group C.
Northern Ireland, which was already eliminated, finished next to last in the group with nine points.
''Now we've got the Euros and we've just got to continue like this,'' said Cassano, who has nine goals for Italy.
Cassano had to apologize after insulting an Italian journalist during midweek training, and he has been on and off the national squad for years due to behavior problems.
''I'm stressed out. I would like to have a good European Championship and a good World Cup and then retire,'' the 29-year-old AC Milan forward said. ''It's 13 years now that whatever I say doesn't go over well. So at 33 I'm going to be finished with football and enjoy my family.''
Nigel Worthington announced on Monday that this would be his final match as Northern Ireland coach, thus ending his 4 1/2-year stint with the national team.
Before kickoff, Italy honored its four players with more than 100 caps: current goalkeeper Gianluigi Buffon, who was making his 110th appearance; retired goalkeeper Dino Zoff (112), former defender Paolo Maldini (126) and record-holder Fabio Cannavaro (136).
Italy will next face Euro 2012 co-host Poland and Copa America champion Uruguay in friendlies Nov. 11 and 15, while Northern Ireland isn't slated to play again until February, giving the Irish FA plenty of time to find a replacement for Worthington.
Italy : Gianluigi Buffon (Morgan De Sanctis, 77), Giorgio Chiellini, Daniele De Rossi, Antonio Cassano (Pablo Osvaldo, 56), Federico Balzaretti, Alberto Aquilani (Antonio Nocerino, 69), Andrea Barzagli, Mattia Cassani, Riccardo Montolivo, Sebastian Giovinco, Andrea Pirlo.
Northern Ireland : Maik Taylor, Lee Hodson, Ryan McGivern, Gareth McAueley, Oliver Norwood (Connor McLaughlin, 74), Chris Baird, Andrew Little, Steven Davis, David Healy (Warren Feeney, 65), Corry Evans, Jonny Gorman (Niall McGinn, 77).