The Germany international scored two goals of immense quality to help inspire the reigning champions back from the dead against Miroslav Djukic's positive side
Some sloppy defending typified the early exchanges, with Manucho putting the hosts ahead early on before Karim Benzema levelled just five minutes later. Manucho added his second from another corner in the 22nd minute but one goal either side of half-time from Mesut Ozil guided the champions to a much-needed victory.
Madrid have been poor on the road so far this season and it seemed as though their woes would continue as some awful marking from a corner enabled the hosts to take a seventh-minute lead. Drawn to the ball, Sergio Ramos left Manucho free in the area and the Angolan pounced on Alvaro Rubio's pass to open the scoring.
However, Valladolid soon became the culprits of some dire defending themselves as Jose Callejon latched onto a short back pass from Omar Ramos. Combined with a slip from Marc Valiente, the Madrid man was able to lay the ball on for Karim Benzema to slot in a simple equaliser.
Los Merengues had responded well to going behind but their good work was undone at the first half's midway point. Patrick Ebert's corner was met by Manucho, who outjumped Ramos at the near post to head his side back into the lead.
Callejon missed a chance to draw level immediately after as his poorly struck lob dropped wide of the goal and on the half-hour mark it was Cristiano Ronaldo's turn. The Portuguese sent a venomous strike at Dani Hernandez's goal but the goalkeeper turned it behind with a strong hand.
Madrid also had a goal incorrectly ruled out for offside as Ramos netted and was penalised despite being in a legal position, even though three of his team-mates were not as the ball was played through.
But the champions' persistence finally paid off on the stroke of half-time as Ozil found Benzema after a mazy run in from the left. The striker held the ball before rolling it back to the German and his effort squeezed under Dani and into the net.
Mourinho took young left-back Nacho off at half-time but in introducing Angel Di Maria, the Portuguese subsequently moved Callejon into the defence.
Despite it being a clear signal of intent from the visitors, Valladolid were unperturbed and a powerful strike from Oscar was unconvincingly kept out by Iker Casillas in the 60th minute.
Mourinho was once more spurred into action and two minutes later he replaced Alvaro Arbeloa with Luka Modric, moving Alonso back into the defence.
It seemed to galvanise his side and Los Blancos' gambles finally paid off with 18 minutes remaining. A cheap free kick was given away by Henrique Sereno and Ozil took a short run up before bending a majestic effort towards the top corner which crashed in off the bar.
Dani made another great stop in the closing stages to keep out Ramos but ultimately Valladolid's run of five games without defeat at home came to an end, with Mourinho's men moving to within two points of second-placed Atletico Madrid in the process.