Karim Benzema netted twice in quick succession before a red card for Casemiro handed hope to Valladolid, but Luka Modric scored a fourth to strengthen Madrid's hold of third position in what could reportedly be Santiago Solari's last game in charge.
The spot kick was followed by Valladolid having two goals disallowed for offside, with Sergi Guardiola's tap in at the back post being ruled out after VAR determined that Keko had strayed beyond the last defender before delivering the cross.
Guardiola was then denied for a second time in quick succession as the forward headed home having gone a second too early with his run, and Madrid were left feeling relieved that they were still on level terms.
Madrid improved as the first half progressed and Benzema went close with a left-footed strike from the edge of the area, but Valladolid finally went in front shortly before the half-hour mark.
A cross from the right was volleyed back across goal by Guardiola, and Tuhami was able to divert the ball into the bottom corner from close range.
However, Madrid were soon back on level terms. Goalkeeper Jordi Masip failed to punch the ball clear from a corner, and Varane was on hand to tap home from four yards out.
Tuhami wasted a chance to put Valladolid back in front by making poor connection with a volley from 12 yards out, while Masip had to react sharply to prevent Casemiro's long-range effort from finding the bottom corner at the other end.
Valladolid were the better side after the restart with Tuhami squandering a chance by poking the ball wide from 10 yards out, but Madrid did not waste any time in completing the turnaround.
Odriozola was upended by Oscar Plano just inside the box, and Benzema made no mistake from the spot as he slotted the ball low to Masip's left.
Dani Ceballos should have extended Madrid's advantage with a volley from 12 yards out, but Masip reacted well to tip the midfielder's effort over the bar.
However, Madrid went further ahead from the resulting corner as Toni Kroos crossed for Benzema to power a header into the bottom corner from 10 yards.
Madrid continued to push forward for a fourth with Valladolid having seemingly been left discouraged, but Guardiola reminded Solari's side that they still had work to do by hitting the post with a volley from a corner.
Casemiro was then dismissed for a second yellow card - given to him for standing in front of a free kick - but Madrid soon confirmed the three points with Modric slotting the ball into the far corner of the net having weaved his way past a defender.
The success may not be enough for Solari to keep his job at the Bernabeu, but the interim manager will be satisfied that his players are ready to at least battle for second place with Atletico Madrid.
REAL VALLADOLID (4-3-3): Masip; Antonito, Fernandez, Calero, Nacho; Tuhami (Verde 63'), Michel, Alcaraz; Keko (Cop 73'), Guardiola, Plano (Unal 86')
REAL MADRID (4-4-2): Courtois; Odriozola, Bacho, Varane (Vallejo 88'), Reguilon (Marcelo 89'); Modric, Casemiro, Kroos (Valverde 74'), Ceballos; Asensio, Benzema