Javi Guerra struck three minutes into the second half to score the only goal of the game and take his team onto 43 points, 11 ahead of the Galicians, who still occupy the final relegation spot.
The game was a tight affair from start to finish, with neither side taking many risks and few openings appearing.
After a first half of no clear chances, the home side made the decisive breakthrough four minutes into the second period.
Patrick Ebert swung in a corner into the six-yard box and Guerra showed great technique to backheel the ball into the net.
Despite Deportivo needing a win to lift themselves out of the relegation zone, Fernando Vazquez's side showed little attacking ambition and managed just two further attempts on goal.
Pizzi sent in a dangerous low cross into the area that just evaded Riki and Nelson Oliveira, while Valladolid goalkeeper Jaime Jimenez tipped away a shot from Bruno Gama that was heading for the top corner.
Depor had the ball in the net with nine minutes remaining as Oliveira stabbed home from two yards out, but the effort was ruled offside.
As the final whistle blew Valladolid coach Miroslav Djukic and his staff ran onto the pitch to embrace the players on securing survival, 11 months after getting back into the top flight via the play-offs.