The Tykes' quest for a goal from one of their own players continues, as an opposition defender, Stephen McManus, opened the scoring by miscuing the ball into his own net in Tuesday's Championship clash.
Scott McDonald levelled six minutes later with a header before Barry Robson snatched the early lead with an easy tap-in.
Marvin Emnes rounded off a frenetic first half as he raced onto a McDonald pass to slot home.
Barnsley manager Keith Hill opted to shuffle his pack, summer recruit Craig Davies dropped to the bench for Scottish striker Jim O'Brien.
Goalkeeper Luke Steele and defender Stephen Foster were passed fit and replaced David Preece and Jimmy McNulty.
Middlesbrough boss Tony Mowbray made one enforced change, Julio Arca replacing the suspended Tony McMahon.
Barnsley's first goal of the season came from an unexpected source in the fifth minute.
Tricky wing play from David Perkins saw the former Colchester midfielder slip the ball into a waiting throng of team-mates in the penalty area. Under heavy pressure to clear, McManus stubbed the ball past an exasperated Carl Ikeme.
The visitors responded almost immediately, McDonald nipping in unmarked to glance Robson's inswinging corner beyond Steele's grasp.
McDonald then tore through a disorganised back line to force the ball into the path of a grateful Robson who clipped the ball home.
Lone Barnsley frontman Danny Haynes beat the offside trap to receive a perfectly weighted aerial pass after 25 minutes, but Ikeme was on hand to sweep up his soft attempt.
Robson came close to doubling his tally moments later, his curling free-kick evading Steele's far post.
Justin Hoyte stormed down the right wing, hurdling Jay McEveley's tackle and picking out Robson in the six yard box.
The Scottish midfielder leapt to make strong contact with the ball but his header bounced high over the crossbar.
Emnes then grabbed McDonald's pass and placed the ball under Steele for his sixth goal in four games just two minutes before half-time.
Middlesbrough were first to threaten after the break, Arca rushing behind the defence but poking tamely into Steele's arms.
McDonald had his head in his hands minutes later when he warmed the goalkeeper's palms when presented with a clear chance to extend the lead.
Perkins then feebly allowed Hoyte to dispossess him on the edge of the Middlesbrough box, to the jeers of the impatient home supporters.
Hill threw Davies into action on the hour mark to add some bite to his strikeforce, but the north east side stood resolute in defence.
Eager to redeem himself for his previous mistake, Perkins then launched an audacious dipping drive at Ikeme's goal but failed to find the target.
Emnes wasted the best late chance on goal, failing to snatch the ball from Steele's feet in a moment of confusion.
As the game entered four minutes of added time, McDonald raced clear behind a tired Barnsley backline but was given offside.