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However, there was a massive double body blow for Fabio Capello's men midway through the first half, first when title rivals Barcelona took the lead away at Gimnastic Tarragona, and then when Van Nistelrooy limped out of the action.
The Dutchman, who was La Liga's leading scorer with 25 goals coming into the game, appeared to have damaged his hamstring and he was replaced just after the half-hour mark by Gonzalo Higuain.
Higuain had scored just twice for Madrid since joining the Spanish giants during the winter break, but he now had the unenviable task of filling the massive gap left by Van Nistelrooy's departure.
The young Argentinian was unable to make much of an impact before half-time though, and things were looking bleak at the break for the title hopefuls with Mallorca still leading and Barca in command at Nastic.
Capello made his second switch at half-time, bringing on playmaker Guti - who the home fans had been calling for in the opening period - in place of Emerson.
Beckham had two chances to show his dead-ball prowess at the start of the second half, although neither resulted in a goal.
The first saw the former England captain's chipped pass headed wide by Sergio Ramos, who should really have done better, while the second saw Beckham curl a direct shot over.
Mallorca had shown little as an attacking force following their goal, but they should have made it 2-0 in the 55th minute.
A cross-field ball cleared Madrid full-back Michel Salgado and allowed Varela to break through on goal. But while his first touch was good, the Mallorca goalscorer fired his shot across the face of goal with only Casillas to beat.
Soon after that Madrid had their best chance of the opening hour, when Beckham's curling free-kick from out wide struck the top of the crossbar before going out for a throw-in.
Beckham was not to have much more of an influence on the game though as he was replaced by Reyes in the 66th minute as Capello made his final throw of the dice.
The move proved to be a masterstroke as within two minutes of his arrival Reyes drew Madrid level.
Higuain turned superbly inside the area before cutting the ball back to Reyes on the edge of the six-yard box, and the Spain winger slotted home right-footed.
With Barca cruising to victory, Madrid knew that one goal would not be enough and the scene was set for a frantic final 15 minutes.
But it was to be a finale to remember for the home side, as quickfire goals from Basinas and Reyes saw the title wrapped up.
Greece midfielder Basinas can count himself very unlucky as there was nothing he could do when Moya palmed Mahamadou Diarra's powerful header on to him while he stood on the post.
The ball clipped Basinas and went agonisingly over the line.
That goal sent the home crowd into delirium, but better was to come as just minutes later Reyes latched into a loose ball on the edge of the box before curling a clinical shot into the corner of the net.
It was party time for the packed Bernabeu after that, with the club's first major title in four years in the bag.
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