Tony Mowbray's side could do little to capitalise on the Saints' 3-0 reverse at Brighton as Blackpool's attacking trio of Matt Phillips, Lomana LuaLua and Thomas Ince ran riot.
All three missed chances to put the Seasiders ahead in a goalless 45 minutes but Phillips was on hand to open the scoring after Barry Robson hit the post for Boro.
LuaLua doubled the advantage shortly before the hour and Seb Hines' first contribution after coming off the Middlesbrough bench was to turn a Phillips pass bound for Ince into his own net.
The win takes Ian Holloway's men to within a point of the play-offs, while victories for West Ham and Cardiff drop Middlesbrough out of the automatic promotion places and down to fourth position.
Tony McMahon and Richard Smallwood came into the Middlesbrough side after knee injuries ruled out Nicky Bailey and Julio Arca.
LuaLua returned in attack as one of four changes for Blackpool, whose captain Barry Ferguson was suspended following his red card in the defeat at Birmingham.
Ince was another addition to the Seasiders' forward line and he started impressively in tandem with LuaLua, shooting narrowly wide from close range and drawing an impressive stop from Boro goalkeeper Jason Steele.
Middlesbrough's best chance of the opening 45 minutes came when Scott McDonald burst clear and rounded Mark Howard in the Blackpool goal, only to find defender Craig Cathcart in attendance on the line.
McDonald then drilled across the face of goal after being played in by Faris Haroun in the 29th minute, but Blackpool's pace in attack continued to cause headaches.
Ince was off-target at the end of a mazy run and LuaLua engineered space before a deflection off Boro defender Matthew Bates sent his shot narrowly wide.
Middlesbrough's defence were relieved to hear referee Scott Mathieson blow the half-time whistle shortly after Angel Martinez sent Phillips rampaging down the right channel to draw a sharp Steele save, before LuaLua's clever cutback narrowly evaded two of his fellow attackers.
The visitors made a more purposeful start to the second period but it was Blackpool who took the lead. Phillips mesmerised the Boro defence before clinically finding the bottom corner from 16 yards.
McDonald's touch let him down in the Blackpool area as Middlesbrough sought an immediate response, and their task became twice as difficult in the 57th minute.
Tangerines full-back Alex Baptiste dispossessed Joe Bennett and drove forward to unleash a stinging drive that Steele saved, but LuaLua was on hand to collect the goal his performance merited.
Haroun then had an effort disallowed for offside before Blackpool put the result beyond doubt with 20 minutes to play.
Hines had only been on the pitch for two minutes after replacing Smallwood and was unfortunate enough to provide the decisive touch on Phillips' cutback with Ince poised to apply the finish.