Ramires opened the scoring in the 11th minute with an incisive run down the right before beating Pepe Reina at his near post with a fierce strike, and Didier Drogba then secured his place in history as he became the first player to score in four separate FA Cup finals with a clinical finish to double Chelsea’s lead just after half-time.
Reds substitute Andy Carroll pulled a goal back with an emphatic shot in the 64th minute following a mistake from Jose Bosingwa, and was denied a second late on as Petr Cech palmed a stunning save off the line with replays showing it was agonisingly close to being the equaliser.
Chelsea held firm in the closing stages to seal a tight victory in a dramatic finale, and the Blues were left to celebrate a fourth FA Cup final triumph in the last six seasons with a Champions League final still to come in Munich.
It was a stunning day for Di Matteo, who became the third Italian manager in three years to win the Cup, after Chelsea's Carlo Ancelotti in 2010 and Manchester City's Roberto Mancini last year, while the result ensured that Kenny Dalglish has just the League Cup to show for his side’s campaign.
Neither Fernando Torres nor Carroll started as both clubs decided to leave their most expensive ever players - at a combined £85million - on the bench for the showpiece, with Didier Drogba and Craig Bellamy given the nod instead. Chelsea also recalled Frank Lampard, Juan Mata and Ashley Cole, while Liverpool brought back Steven Gerrard, Luis Suarez, Jose Reina and Daniel Agger, with Jamie Carragher missing out.
Ashley Cole, who won the cup three times with Arsenal and has three winners' medals with Chelsea, saw a lot of the ball early on as the Blues kept the majority of the possession in the opening 10 minutes with neither side creating a chance.
But one of the Chelsea players suspended for the Champions League final sparked the game into life as Ramires latched on to a through ball from Juan Mata before brushing aside the obliging Jose Enrique and catching Reina out at his near post with a ferocious shot.
Three minutes later, Bellamy almost capitalised on a loose ball in the Chelsea box as Branislav Ivanovic failed to clear with a stooping header, but the Welshman's shot was blocked away by the Serb, who swiftly made amends.
Chelsea, playing in the FA Cup final for the fourth time out of a possible six at the new Wembley, looked the more comfortable in the opening stages, while Liverpool’s midfield appeared devoid of ideas.
It was a fairly tepid first half, with both sides unable to stamp their authority on proceedings, Ramires’s marauding run was an exceptional moment in a simmering contest.
Jordan Henderson almost carved out a clear-cut opportunity for Suarez with a precise dinked delivery from the right, but the forward had little time to direct his instinctive header wide of the far post with Petr Cech able to shepherd the ball out of play.
The last side to win the FA Cup final after trailing at half-time were Liverpool against West Ham back in 2006 and the onus was firmly on Dalglish’s side to respond at the start of the second half.
But it was Chelsea who made a huge impact seven minutes after the restart through a familiar source: Drogba latched on to a through ball from Lampard and unleashed an unerring low drive past Reina to beat the Liverpool goalkeeper at his far post.
It was Drogba’s 11th goal against Liverpool and, excluding the Community Shield, he has now scored in all eight of his matches at Wembley.
But Liverpool responded in style as substitute Carroll turned Terry inside out inside the Chelsea box before firing an emphatic finish into the roof of the net after Bosingwa dallied on the ball out wide to squander possession.
Carroll, who has scored four goals in six FA Cup appearances this season, clearly buoyed Liverpool with his goal and Chelsea were promptly forced to weather a storm of pressure from their opponents.
There was further drama with eight minutes remaining as Carroll headed powerfully on target from the back post, forcing a stunning save from Cech, who palmed the ball off the line with it perilously close to crossing for a goal. Liverpool and Carroll were convinced that it was a goal, but replays suggested that the entirety of the ball had not crossed the line to vindicate the assistant referee’s crucial decision.
Chelsea were left to cling on desperately to preserve their slender one-goal advantage and deny Liverpool a second cup triumph this season.
The Blues, however, may yet manage to win a second cup, with the Champions League final with Bayern Munich a fortnight away.