Patrick Ebert opened the scoring with a little over a minute on the clock and quickly set up the second for Oscar Gonzalez as the visitors started strongly.
Manucho's own goal put the game back in the balance but Sevilla then had Gary Medel sent off and, despite some late pressure, could not muster an equaliser.
Valladolid were swiftly out of the blocks, with Oscar playing in Ebert to beat keeper Diego Lopez from 12 yards.
And Ebert wasted little time in returning the favour as his through-ball in the 12th minute was finished from close range by Oscar to make it 2-0.
Jose Antonio Reyes had Sevilla's first two efforts, a left-foot effort saved by Daniel Hernandez and a free-kick into the wall, either side of a Manucho effort for Valladolid which was inadvertently blocked by team-mate Marc Valiente.
Jesus Navas shot wide before Sevilla coach Michel decided he had seen enough and changed his tactical approach, midfielder Bryan Rabello replacing defender Cicinho.
Oscar headed Omar Ramos' free-kick wide before Medel and Rabello threatened at the other end, the substitute drawing a save from Hernandez.
Ebert's free-kick was saved and, in first-half stoppage time, Manucho fired over.
The former Manchester United man made an unwanted contribution at the other end early in the second half, though, to gift Sevilla a route back into the match.
From Reyes' right-wing free-kick, Juan Cala's header was blocked behind for a corner. Ex-Arsenal winger Reyes took that as well and Manucho could only divert the ball into his own goal.
Navas' shot was saved and Oscar fired over at the other end before Sevilla's attempts to get themselves back in the game were undermined by Medel's dismissal.
The volatile midfielder collected his second yellow card for a foul on Manucho, with Ebert almost exacting further punishment as his free-kick forced Lopez to tip the ball around the post.
Reyes twice threatened an equaliser in any case, though Manucho missed a chance to make the game safe at the other end.
Valladolid's Jesus Rueda blocked shots from Diego Perotti and Reyes as the hosts continued to press even while playing a man short.
Alex Rubio and Papa Diawara both missed close-range chances before Reyes was again denied by a block from a defender, this time Valiente.