Two goals from Freddie Ljungberg knocked Middlesbrough out of the FA Cup and justified Arsenal manager Arsene Wenger's gamble to rest top-scorer Thierry Henry.
Ljungberg restored Arsenal's lead after Joseph-Desire Job cancelled out Dennis Bergkamp's goal - then struck again to put the Gunners out of sight. Nineteen-year-old forward David Bentley stepped off the bench to add the fourth.
Boro finished with ten men after midfielder George Boateng was sent off in the closing minutes after collecting a second yellow card.
Arsenal were without injured strikers Sylvain Wiltord and Jeremie Aliadiere, while Kanu is away with Nigeria at the African Cup of Nations.
But Wenger said: "I had to rest Thierry at same stage. He's played in virtually every game and up front that's a difficult job. It's physically demanding so it's important for him to have a break.
"I left Thierry out at the same time last year. Looking at the fixtures, the only opportunity I had to do it was in this game. I was confident that we could win without Thierry because our team is known for playing well as a unit.
"Our passing and movement were first class. We always looked like we could open them up. Freddie was the Fox-in-the-Box for us. He made some great runs. It was also good for the fans to see two promising young players - Bentley and Gael Clichy - come on.
"We've played Boro so often lately it seems like we're seeing them more often than our families - so we're delighted to avoid a replay." He added: "The FA Cup is important to us. We've played in four finals in the last six years and only lost once. We have a special bond with this competition." Arsenal have not lost an FA Cup tie since their 2-1 defeat by Liverpool in the 2001 final, and they will hope that this win proves a happy omen. The Gunners beat Boro on the way to the FA Cup final in 1998 and 2002 - when they won Premiership and Cup doubles.
Boro, beaten finalists in 1997, have yet to win a major trophy in their 129-year history, while boss Steve McClaren has lost eight of his nine games in charge against Arsenal.
This was the third episode of a four-match series between the clubs in 18 days. Arsenal cruised to a 4-1 Premiership win in the first game, but Boro beat a weakened Gunners side 1-0 in the Carling Cup semi-final first leg on Tuesday.
Both teams were much-changed from then. Bergkamp returned after a calf injury for Arsenal, while Jens Lehmann, Lauren, Ashley Cole, Patrick Vieira, Robert Pires and Ljungberg were restored after sitting out the Carling Cup tie.
Boro were forced to rearrange again at the back. Ugo Ehiogu, their rock on Tuesday, was sidelined by a groin strain. Gareth Southgate and Colin Cooper were already ruled out by hamstring knocks.
Their absence placed a big responsibility on Danny Mills and Chris Riggott. Defensive midfielder Doriva was suspended, while McClaren surprisingly dropped Tuesday's matchwinner, Juninho and strike partner Massimo Maccarone, in favour of the more physical Michael Ricketts and Job.
Ricketts' pace and power caused early problems for Kolo Toure, whose mis-kick under pressure almost let in Bolo Zenden, before Jens Lehmann rushed out to tidy up.
Pires and Ljungberg pressed forward from wide positions to support Bergkamp, posing Boro's centre backs the problem of who to pick up.
Ray Parlour, chasing a place in his sixth FA Cup final, sent in Arsenal's first shot, an eighth-minute effort wide from the edge of the box, before an offside flag denied the home side a 15th-minute lead after Pires tucked away Bergkamp's throughball.
Four minutes later, Bergkamp fired the Gunners in front. Parlour chased down Edu's pass and whipped a centre past Franck Queudrue for the Dutchman, who fired a drive that deflected off Danny Mills past keeper Mark Schwarzer.
The lead lasted just four minutes until Ricketts won another header, allowing Job to take the ball on his chest and volley home on the turn.
Schwarzer then made a flying save to tip away Cole's curling shot, before referee Mike Dean turned down Arsenal's penalty appeals as Pires went down under Riggott's tackle.
Middlesbrough survived until the 28th minute, when they only half-cleared Sol Campbell's header and Ljungberg controlled Vieira's pass with a clever drag back that gave him the space to bury a low shot.
Boro tried to rattle Lehmann with physical pressure at dead ball kicks and referee Dean lectured the Arsenal keeper for over-reacting to Mills' challenge. But the visitors rarely threatened the German from open play.
Schwarzer grabbed Edu's left-footed free-kick after Zenden was booked for a 36th-minute foul on Vieira, and the Boro keeper denied Bergkamp three minutes after the interval, parrying his angled shot.
Boateng shot wide from 20 yards as Boro tried to fight back, but Riggott and Stuart Parnaby were booked for fouls as Arsenal turned up the pressure.
Ljungberg effectively ended Middlesbrough's resistance after 68 minutes. Bergkamp's shot was deflected for a corner. Boro's defence went to sleep as Pires swung in the kick and the Swede arrived unmarked to score with a close-range header.
McClaren made a triple 73rd-minute attacking substitution, sending on Juninho, Maccarone and Szilard Nemeth for Stewart Downing, Job and Ricketts. It was a desperate measure.
His side's hopes were finally sunk by Boateng's dismissal four minutes from time. Referee Dean reached for the red after the Dutch midfielder fouled Parlour - Boateng had been booked two minutes earlier after a tackle on Pires.
Substitute Bentley piled more misery on Boro. The young striker clipped a 20-yard shot beyond Schwarzer as stoppage time approached - his first senior goal for the Gunners.
Now to the Riverside for the Carling Cup semi-final second leg on Wednesday. Which team will Wenger field then? MAN OF THE MATCH: Freddie Ljungberg showed flashes of his razor-sharp finishing of two years ago to score two vital goals.