Uche Ikpeazu scored his first goal in Chairboys colours, as Middlesbrough scored three under the floodlights at Adams Park.
Wycombe were the first to strike with a fantastic goal from Uche Ikpeazu, who hit a quality shot into the top corner to put the Wanderers in-front after just three minutes.
Boro grew into the game though and got two quickfire goals just before the break, the first from Marcus Browne nodding in from a set-piece and the second from Marcus Tavernier who found the bottom corner.
After the restart, Wycombe were much better as they hit the bar twice, but Middlesbrough clinically found their third through Chuba Akpom to settle the game.
Gareth Ainsworth went with the same starting side that beat Cardiff City midweek, with only one change, former Boro’ player Alex Pattison coming in for Darius Charles on the bench.
In the first-ever league meeting between the sides, the ball had barely been on the ground in the early stages, but with a moment of magic, Uche Ikpeazu opened the scoring with a fantastic strike.
Wycombe’s number nine scored his first-ever goal for the club by cutting inside and sweetly hitting a rocket into the top-left corner.
There was little action immediately after the first goal, with both sides battling for supremacy.
Middlesbrough did get a few chances, with one leading to a corner. Northern Irish international, Paddy McNair, delivered the set-piece towards Marcus Browne who levelled the score with a header with half-an-hour played.
The away side used the momentum to score the next goal soon after through Marcus Tavernier. The winger ran with the ball, skipped past his man and finished into the bottom corner to make it 2-1.
Wycombe came close to equalising a few minutes later when Daryl Horgan picked out Anis Mehmeti, but the 19-year-old's shot was straight at Marcus Bettinelli. That meant that the away side went into the break in the lead.
After the restart, Middlesbrough had a good chance to score their third early on, but Tavernier could only head the ball over the bar from close range after a good delivery from Marvin Johnson.
In what was nearly a repeat of Wycombe’s first goal against Cardiff, Jacobson delivered a corner to Ryan Tafazolli but this time he just headed the ball over the bar.
In Scott Kashket’s first involvement since being substituted on, the striker struck a deflected shot that hit the crossbar. The resulting corner fell to Ryan Tafazolli and his header was clawed off the bar for a second time by the keeper.
Meanwhile down the other end, Horgan was called into action to head off the line to stop Middlesbrough scoring a third.
Tavernier had a chance to put the game out of sight a few moments later, but his powerful strike came off the crossbar and back off the goal line, with the technology confirming no goal.
Middlesbrough did get one final chance as McNair put in one last corner which came directly off the post and fell to Chuba Akpom, who was there to tap it in as the game finished 3-1 to Boro.
Wycombe’s next game is against Preston in the FA Cup.