Paco Alcacer gave Luis Garcia's side an undeserved lead moments before half-time but goals by Oscar Ramos and Javi Guerra in quick succession turned the match around, before Alexis Ruano was sent off for Getafe.
The hosts dominated both halves but took their time in making their superiority count.
Daniel Larsson troubled Getafe goalkeeper Jordi Codina early on when he shot through a crowded penalty area, but the goalkeeper got a hand to it and Manucho failed to take advantage of the rebound.
Lluis Sastre later headed a free-kick just wide of the near post and Patrick Ebert hit a dangerous shot over the bar following a lovely combination with Oscar.
Manucho had a chance to give his side the lead before the break after Oscar gave him the ball with a backheeled pass following a brilliant through ball by Ebert, but the forward hesitated before eventually shooting wide.
The Angolan did not enjoy the best of afternoons and was substituted with 25 minutes remaining.
Despite all the pressure form the home side, it was Getafe who broke the deadlock right on half-time.
Borja Fernandez played a long ball into the box and Paco Alcacer beat the offside trap and got beyond the defence to aim a glancing header over Dani Hernandez and into the net.
Valladolid continued to take the initiative in the second period but could have fallen further behind had Alexis not squandered a great chance to score by shooting wide.
Miroslav Djukic's side eventually got the goal their performance deserved after 67 minutes when Oscar headed a cross by Alvaro Rubio beyond Codina.
The scorer then became the provider of the winning goal. Oscar played a long ball up to substitute Javi Guerra, who brought it down with his chest, took one touch and then shot into the bottom corner.
Getafe were reduced to 10 men with 14 minutes left when Alexis was sent off for elbowing Ebert while contesting a header.
However, they still managed to create chances in search of an equaliser, the best of which fell to Diego Castro in stoppage time, but the forward failed to hit the target.