Real Madrid moved up to third in La Liga after beating Sevilla 2-0 at the Santiago Bernabeu on Saturday.
Casemiro broke a tense deadlock with a spectacular strike from distance in the 78th minute, before Luka Modric ultimately sealed the points in stoppage time.
Los Blancos added to last week's impressive win away to Real Betis and all but ended Sevilla's slim title hopes.
Santiago Solari hasn't liked to start Isco since the manager grabbed the reins in October. Yet it took just 13 minutes for the former Malaga schemer to prove why he should be in the first XI more often.
Isco entered the fray as a 77th-minute substitute for Lucas Vazquez and immediately quickened Real's pace of play. Frankly, it was odd Solari had waited so long to bring Isco off the bench after how uninspired Real looked during the opening half.
The hosts went from tepid to vibrant with Isco on the pitch. His trickery, quick feet and intelligence won free-kicks, created chances for others and manufactured shooting opportunities for himself.
Seeing Isco make such a subtle yet significant difference makes one question why Solari doesn't trust him more. Even with Toni Kroos out with a thigh injury, Dani Ceballos got the start.
Ceballos simply hasn't proved good enough to refresh things in the middle since he signed from Real Betis in 2017.
By contrast, Isco can enliven an increasingly bland style of play.
Real's experienced midfield is still workmanlike enough to take narrow wins at home. However, the group needs more creativity and fresh guile if it's going to continue to help deliver major trophies.
Sevilla host Barcelona in the first leg of a Copa del Rey quarter-final on Wednesday before a league home game against Levante next Saturday.
Real are also in cup action at home to Girona in the last eight on Thursday ahead of a return to league action away to Espanyol next Sunday.