The strikeforce of Yakubu and Mark Viduka sent the home fans happy, even though referee Chris Foy was involved in another controversial penalty incident before half-time.
The win will have given tremendous relief to rookie manager Gareth Southgate after a traumatic first half of the season.
Before the kick-off Middlesbrough fans unveiled a large banner in tribute to chairman Steve Gibson.
The banner had the words "One of us" and a giant photograph of a popular chairman who has been the most influential figure behind the scenes for two decades.
Fans' spokesman Geoff Thomas said before the game: "The banner first and foremost acknowledges the enormous debt of gratitude Boro fans the world over owe Steve Gibson.
"Through the design and words it is hoped the banner will act as a binding visual reminder to the club's fans of the core values Steve represents - passion and commitment."
Middlesbrough made two changes following the 2-1 defeat at Blackburn Rovers, while Sheffield United made six changes after the superb 1-0 triumph over Arsenal.
Yakubu had a shot deflected for a corner in an early Middlesbrough attack.
Middlesbrough midfielder Lee Cattermole was booked for a foul on Chris Armstrong after 15 minutes. The challenge angered United manager Neil Warnock on the touchline and he vented his feelings.
England winger Stewart Downing and Julio Arca were both off target for Middlesbrough after 28 minutes Keith Gillespie was responsible for United's first scoring effort but from his free-kick Mark Schwarzer made a full-length save.
There were limited thrills for the fans with a lack of midfield flair from both teams.
Middlesbrough lost Jonathan Woodgate when the England defender walked off after 32 minutes. Stuart Parnaby took over at right-back with Abel Xavier moving to the heart of the defence.
The home side went ahead after 36 minutes when Viduka received a pass from Arca and turned on the edge of the penalty area before leaving goalkeeper Paul Gerrard helpless with a left-foot shot.
Just when it looked as though Middlesbrough would go into the break with a lead, the referee awarded the Blades a controversial penalty.
Earlier in the season Mr Foy awarded Manchester United a penalty on an occasion when Middlesbrough players claimed Cristiano Ronaldo took a dive.
On this occasion his decision against defender Emanuel Pogatetz looked extremely harsh and to rub salt into the wounds Phil Jagielka beat Schwarzer from the spot.
Middlesbrough were clearly affected by the penalty decision and United could have piled on the agony in injury-time but for clearances by Arca and Andrew Taylor.
However, after 68 minutes Yakubu put Middlesbrough into the lead. The Nigeria international provided the finishing touch, although his team-mates congratulated Viduka whose shot was destined for the net.
Middlesbrough made certain of the points with a Yakubu penalty after 76 minutes. The referee ruled Chris Morgan had fouled Yakubu but United did not look happy with the decision.
Yakubu maintained his reputation as a penalty king when he sent Gerrard the wrong way.