Sporting stunned the Bernabeu when David Barral scored against the run of play in the 53rd minute but it only took Manuel Pellegrini's side two minutes to equalise.
Rafael van der Vaart and Xabi Alonso struck in quick succession before Gonzalo Higuain calmed the nerves with a superb solo effort in the 68th as Real claimed their 14th win in 14 home games this season.
"We only have the league left to fight for and we have the responsibility to win every day," Real midfielder Esteban Granero told reporters.
"We lacked fluidity in the first half but when they scored it stung us and we knew how to react."
Dutch international Van der Vaart appeared to control the ball with his hand before scoring, after Juan Pablo could only parry Cristiano Ronaldo's free-kick.
Sevilla's surprise Champions League exit to CSKA Moscow in midweek appeared to have taken a heavy physical and mental toll as they were well beaten at lowly Espanyol, Argentine striker Pablo Osvaldo scoring a goal in each half.
Manolo Jimenez's side lost wingers Jesus Navas and Diego Capel to injury during the game and remain on 44 points, three points behind third-placed Valencia who are in the final automatic Champions League qualifying spot.
It was Valladolid's first win in 12 matches and the first under coach Onesimo Sanchez, who replaced Jose Luis Mendilibar at the beginning of last month.
