Confident Arsenal brushed aside lacklustre Boro to go level with Manchester United at the top of the Premiership.
Both teams have 49 points and an identical goal difference. United have a game in hand.
Robert Pires and Freddie Ljungberg added second-half goals for the Gunners after Thierry Henry made the breakthrough from the penalty spot and Franck Queudrue conceded an own goal. Only Massimo Maccarone's late penalty denied Arsenal outright leadership.
Happy Arsenal manager Arsene Wenger said: "It was a very good performance, a complete team performance. We were solid at the back and creative in attack. We were very strong until we were 4-0 up.
"We made a lot of chances early in the game. (Jeremie) Aliadiere and Henry were close inside the first two minutes, but we never got frustrated when we didn't score.
"We kept playing our football, kept creating chances, because we were confident that the goals would come."He added: "We've had memories of letting leads slip, at Leicester and at Everton on Wednesday. That wasn't the case this time. Our second goal, just before half-time, killed the game. It was difficult for Middlesbrough then and we kept up the pressure in the second half."Boro boss Steve McClaren said: "It's our first away defeat for months. It's disappointing that a good run has ended, but we have no excuses.
"We didn't pass the ball well, we defended poorly and got punished. Now we have to lick our wounds and come back stronger."Arsenal remain the only unbeaten side in the Premiership. Defeat drops Middlesbrough to 14th place and back towards the relegation dogfight. They are only five points ahead of the bottom three.
Boro and McClaren must be sick of Arsenal. They have won only once at Highbury since 1939. McClaren has lost all his seven league and cup games in charge against the Gunners. Arsenal had already beaten Boro 4-0 at the Riverside in August.
Arsenal announced their intentions within 40 seconds. Aliadiere broke through on the right of the box and hit an angled shot. Boro keeper Mark Schwarzer saved at full stretch with his left foot.
Henry was next to test Schwarzer, 90 seconds later. He collected Ashley Cole's pass and curled a bending shot that the keeper tipped away for a corner.
The Gunners' pressure continued with a Patrick Vieira header over the bar and another Henry curler, caught by Schwarzer.
Boro, who started with Juninho on the bench, sat back in defence, with George Boateng and Doriva protecting their back four. Doriva moved forward in the 12th minute to fire their first effort, a 30-yard swerver held by Jens Lehmann at the second attempt.
Gilberto Silva was booked for a 20th-minute foul on Boudewijn Zenden as Arsenal's frustration briefly bubbled. Boro's confidence briefly rose after surviving the Gunners' early assault. Their false sense of security was soon to be breached.
The home side continued to press. Ljungberg shot weakly at Schwarzer after Pires found him on the edge of the box. Pires fired over from the same distance.
A 38th minute penalty broke down Boro's resistance. Vieira went down under Ugo Ehiogu's clumsy challenge. Referee Andy D'Urso pointed to the spot and Henry drilled the kick low past Schwarzer.
Middlesbrough spent the rest of the game trying to limit the damage.
Aliadiere wasted a quick break with a misplaced cross, then Henry's deflected 35-yard free-kick bounced off an upright.
Arsenal struck again in first-half stoppage time. Boateng fouled Pires, Henry hit the free-kick from 20 yards and his shot ricocheted home off defender Queudrue.
Zenden blazed over in a rare Boro attack as the second half opened. The introduction of Juninho and striker Maccarone hardly lifted them either.
The prolific Henry-Pires partnership created Arsenal's third, after 57 minutes. Henry's cross was only half-cleared by Gareth Southgate and Pires sidefooted home the loose ball.
Substitute Nwankwo Kanu made the fourth, 11 minutes later, checking a dribble to pick out Ljungberg who drove a low shot beyond Schwarzer's dive.
Maccarone netted an 85th-minute reply for Boro, tucking away a penalty after he was brought down by Lehmann. It was no more than a consolation as the home side eased up.
Arsenal and Boro will meet again this month, in the FA Cup and two-legged Carling Cup semi-final. The Gunners will have Dennis Bergkamp, Sylvain Wiltord and Kolo Toure back from injury for those games too.
Wenger said: "The way we played will have a psychological effect on the other matches."Boro defender Ehiogu added: "Each game will be slightly different. Arsenal will be favourites every time. Hopefully that will help us to relax and maybe help produce a shock."Boro must find more creativity if they are to spring that surprise.
Defence is Boro's strength. They went seven matches in November and December without conceding a goal. If they concede the first goal though, they rarely come back. They have shown that against both Manchester United and Arsenal in the past month.
They lack a regular scorer, despite McClaren's frequent permutations, while Juninho has failed to show the sparkle of his first spell at the Riverside.
Now they must dread the prospect of more misery at Arsenal's hands.
Man of the Match: Thierry Henry, a class act and constant danger, with his movement in open play and his persistent threat from dead-ball situations.