Los Blancos have collected four points from their opening two matches, both on their travels, while Valladolid are winless in their three matches so far.
That came on the back of a goalless draw with Real Sociedad on the opening weekend, making the second-half comeback at Estadio Benito Villamarin all the more important.
It is now 13 league games without defeat for Madrid post-lockdown, 11 of those ending in victory, with the champions making themselves incredibly tough to beat.
Los Blancos are 11 without defeat against Valladolid, too, in a run stretching back to November 2008, although they were held 1-1 in their most recent home encounter.
Barcelona's big opening-game win against Villarreal on Sunday has laid down a bit of a marker for Zidane's men, while Atletico Madrid also looked impressive in their league bow.
A tight title tussle can surely be expected this term, meaning that dropped points in a fixture such as this one could prove pretty disastrous for Madrid further down the line.
Valladolid hardly enter this fixture in the best of form, though, having kicked off the 2020-21 campaign with two draws and a defeat.
Their home meetings with Real Sociedad and Celta Vigo finished in 1-1 draws, either side of a 2-0 reverse at Real Betis in their only away match thus far.
Valladolid have now lost four and draw one of their last five away league matches, and have won just twice on their travels in the past year.
Sergio's side finished a respectable 13th last season, but if they are to match or better that achievement then they will need to quickly get some wins on the board.
Real Madrid La Liga form: DW
Real Valladolid La Liga form: DLD
Eden Hazard has not been involved in Madrid's opening two matches because of an ankle problem and remains a major doubt for this clash.
Real Madrid possible starting lineup:
Courtois; Carvajal, Varane, Ramos, Mendy; Valverde, Casemiro, Modric; Isco; Vinicius, Benzema
Real Valladolid possible starting lineup:
Jimenez; Perez, Gonzalez, Sanchez, Garcia; Michel, Perez; Hervias, Plano, Rubio; Guardiola
We say: Real Madrid 3-0 Real Valladolid
Madrid have not quite clicked into gear yet but they enter this first home fixture of the campaign as strong favourites. Valladolid tend to struggle on their travels and we are going with a routine victory for the champions on Wednesday.