Nicklas Bendtner stunned the Spaniards with an 18th-minute opener to put Arsenal ahead but Messi levelled within three minutes with a superb drive.
Pedro teed the Argentine up for his second and a cool lob completed his first-half hat-trick in some style.
Messi put the seal on victory with a late solo strike for his fourth.
The 6-3 aggregate win sets up an intriguing semi-final meeting with Jose Mourinho's Inter Milan, although in this kind of form few teams will be capable of preventing Messi and Barcelona from retaining the trophy.
Arsenal, though, more than played their part in a superb quarter-final tie, having come from 2-0 down in the first leg to lead 3-2 on aggregate in the Nou Camp.
Theo Walcott's introduction at the Emirates had rescued the Gunners and his reward for that blistering late cameo was a starting place in the return.
However, Barcelona boss Pep Guardiola anticipated his inclusion by bringing in the pacy Eric Abidal for Maxwell after the full-back was given a torrid time in the first leg.
But predictably it was Barca who carried the early threat as Messi, playing a more central role than in the first leg, hit a low sighter that Manuel Almunia did well to push round the post at full stretch.
The Argentine then served further notice of his ominous threat with a delightful curling shot that dropped on to the roof of Almunia's net.
Just as Barcelona appeared to be gaining a stranglehold though, Arsenal stunned the hosts with a breakaway opener.
Abou Diaby, lucky to escape an early booking for a chop on Xavi, looked to have fouled Marquez on the halfway line but was allowed to play a delightful pass in behind Abidal and send Walcott scampering clear.
Walcott resisted the temptation to shoot, instead teeing up Bendtner for a bundled effort that was blocked by Victor Valdez, only for Bendtner to quickly scramble back to his feet and steer home the opener.
Moments later, Diaby had another chance to play in Walcott as Arsenal broke again, but chose the wrong option as he made a mess of his attempted pass to Bendtner.
It was a costly error, as Barca were back on level terms within three minutes.
When Messi looked to play in Xavi he found Mikael Silvestre in the way, but the Frenchman's touch was poor and he could only steer the ball back into the path of Messi, who brutally lashed home the leveller.
It was the start of a devastating 20-minute spell from the magical Messi and Arsenal found him impossible to contain.
Medieval-Evil
Messi threatened again when he shot into the side-netting after Rosicky had lost possession in midfield, but Barcelona were back in front on 32 minutes after Messi opened up Arsenal with a perfectly-weighted pass to send Abidal clear down the left.
His low cross was cut out by the sliding Thomas Vermaelen but fell kindly for Pedro to tee-up Messi, who finished the move he had started with two touches to steer the ball beyond a mesmerised Almunia.
Messi's fourth hat-trick of 2010 was completed five minutes later, when Seydou Keita's header from the halfway line sent the Argentine clear again for the best finish of the night, a delicate left-foot lob over the stranded Almunia that left Barca in total control - and Arsenal seeing stars at half-time.
Gunners boss Arsene Wenger was presented with a tantalising dilemma over whether to twist or stick - he knew that pushing too hard for the goal that could rescue the tie could leave his side vulnerable to a real hammering at the hands of Messi - and the second half drifted into obscurity as a result.
The disappointing Tomas Rosicky lifted a shot high over the bar and Bendtner's blushes at heading Clichy's brilliant cross against a post were spared by a linesman's flag for offside, but inevitably it was left to Messi to have the final say.
It was from his quick free-kick that Pedro dropped a clipped finish just wide of the far post, but Messi did it all himself two minutes from time when he shrugged off lame challenges from Emmanuel Eboue and Vermaelen before completing his first four-goal haul with a low drive after Almunia had blocked his initial shot.
By Stuart Roach
Story from BBC SPORT:
http://news.bbc.co.uk/go/pr/fr/-/sport1/hi/football/europe/8602344.stm
