Four alterations from Saturday's win over Real Betis saw Zinedine Zidane recalling Marcelo, Alvaro Odriozola, Isco and Luka Modric back to the starting eleven.
Marcelo almost made an instant impact as a trademark foray from the left coincided with Federico Valverde who had Valladolid goalkeeper Roberto Jimenez at full stretch.
Los Blancos were presented with another clear chance to go in front towards the 20th minute, but Luka Jovic failed to rifle in Valverde's cross from the right after good work from Modric.
The home side finished the half the strongest with Modric combining with Jovic to carve out a chance which the latter blazed into the side-netting.
Los Blancos' first-half dominance overlapped into the second half when Jimenez stupendously kept out Jovic' header off a corner whilst the follow-up from Casemiro crashed onto the crossbar.
Excellent piece of goalkeeping from Madrid goalkeeper Thibaut Courtois on 54 minutes parried Shon Weissman's promising looking strike from the bottom corner.
A trio of changes from Zinedine Zidane's side on 58 minutes saw Vinicius Junior, Marco Asensio and Dani Carvajal filling in for Isco, Odriozola and Jovic.
The defending champions got their noses in front 65 minutes in as Vincius got goal-side in the area to dink over Jimenez, with the Video Assistant Referee (VAR) ruling out any offside calls.
Valladolid began to up the ante as full-time dawned with Courtois reduced to acrobatic saves off efforts from Raul Garcia and Waldo Rubio.
Madrid weren't left behind after poor handling from Jimenez led in Modric, who hit the foot of the post while Vinicus was denied a brace late on by Jimenez, with the the Brazilian's solitary strike securing three points.