The Nigerian striker helped Mark Viduka's 69th-minute effort over the line then converted a 76th-minute penalty to wrap up three points and hint at a brighter new year ahead.
Boro were on the brink of squandering more precious points when Phil Jagielka swapped his goalkeeping gloves for shooting boots and equalised an early Viduka strike from the penalty spot.
But the Blades' brilliant win over Arsenal soon became a distant memory as Boro stepped up a gear and consigned Neil Warnock's men to a long battle to escape a relegation dogfight.
Warnock might have expected his side to start brighter, given the six changes he made to his side, including bringing back big guns Rob Hulse, Danny Webber and Michael Tonge.
But their fresh legs failed to provide much impetus and it was the home side who looked most likely to take control of the game with an early goal.
Yakubu fashioned a fine chance in the fifth minute when he bustled past Claude Davis and unleashed a powerful drive from the edge of the box which was deflected just wide by Chris Morgan.
Moments later Boro came even closer as Yakubu fed the recalled Julio Arca, who fired a low shot from 20 yards which flashed inches past deputy goalkeeper Paul Gerrard's left-hand post.
Finally in the 15th minute the visitors made their first foray into the Boro box when Jagielka chased Chris Armstrong's long ball but Arca got there first to shepherd it back to goalkeeper Mark Schwarzer.
Slowly coming more into the match, the Blades enjoyed a period of possession without creating chances, and frustration was already setting in amongst some of the Boro support.
The Blades had their best chance in the 29th minute after Jonathan Woodgate fouled Hulse on the edge of the box. Keith Gillespie's free-kick was tipped low around his post by a diving Schwarzer.
Viduka's clever back-heel in the box in the 32nd minute set up a shooting chance for Yakubu who blazed his powerful drive over the crossbar from close range.
The Australian grabbed the lead in style in the 36th minute when he cleverly turned Robert Kozluk on the edge of the Blades box before firing his fourth goal of the season low past Gerrard.
Hulse won his controversial penalty in stoppage time after being pushed by Emanuel Pogatetz in the box, and Jagielka stepped up to sweep a confident spot-kick to Schwarzer's right and bring the Blades level.
And things might have turned out differently if Arca had not hacked Morgan's powerful header off the line even deeper into added time at the end of the first half.
But Yakubu continued to pose a constant threat and he fired a long-range effort over the crossbar in the 52nd minute after an explosive run across the Blades defence.
Stewart Downing had a good chance on the hour, when Yakubu turned provider on the right flank and crossed for the England man who directed his shot just wide of Gerrard's right-hand post.
Boro's persistence paid off in the 69th minute when Viduka raced into the box and shot under Gerrard from a tight angle, before Yakubu made sure by poking the ball over the line.
And the Blades' challenge was effectively blunted in the 76th minute when Morgan was penalised for tugging Yakubu's shirt in the box and the Nigerian striker got up to sweep home Boro's third from the spot.