The Spain midfielder scored the opening goal at Malaga with a fantastic free-kick and also bagged an assist for Casemiro in a lovely move later on.
It was a very different Real Madrid on Sunday. With Gareth Bale and Cristiano Ronaldo rested, Los Blancos' attacking play was measured, their build-up play owing more to technique and patient passing than speed and physicality. Isco was at the heart of it all.
The 25-year-old midfielder has endured some tough times this season, but when he is at his best, he is a joy to behold and some of his football at Malaga was wonderful.
Real won this fixture 2-1 on the final day of last season to claim the title. There would be no repeat of that success this time around, with Barcelona running away with La Liga, but a victory by the same scoreline at La Rosaleda at least moved Madrid back up to third place in the table with six rounds remaining.
Isco opening the scoring with a fantastic free-kick, curled up an over the wall and into the bottom corner. It was the first time he had netted from a set piece for Real in seven attempts in La Liga and will have left many to wonder why he does not take them more often.
But there was no real celebration. Isco, born in Benalmadena just outside the Andalusian city and also a former Malaga player before joining Madrid, lifted his arms to apologise to the club's fans, supporters who idolised him not so long ago.
Despite a plucky performance against a Real side playing in second gear, Malaga remain rooted to the bottom of La Liga with just 17 points and are extremely unlikely to avoid relegation now.
And having set Madrid on their way to a 100th win under Zidane in all competitions, Isco was also involved in his side's second goal as he squared for Casemiro to complete a lovely team move that the Brazilian had himself started by winning back the ball in midfield.
Against Malaga, Isco scored and assisted in the same game for Los Blancos for the first time this season in all competitions, while he also won four fouls and had more key passes (three) than any other player in the game at La Rosaleda.
Malaga grabbed a consolation right at the end through Diego Rolan, but Madrid held on for a win and, by that time, Isco had already left the pitch to a rousing ovation from both sets of supporters.
Such showings will do the midfielder's chances of featuring in the Champions League semi-finals against Bayern Munich no harm at all, while his performance and the way Madrid played also gave a glimpse into a future without Ronaldo and Bale.
Real have now won each of their last eight league games when those two have not played, scoring 28 goals in the process. And although Ronaldo is in the best scoring form of his life, he cannot go on forever, while Bale's future looks bleak after he was withdrawn at half-time against Juventus on Wednesday.
Malaga's loss was definitely Real's gain and Isco, still only 25 despite spending five years already at the capital club, can lead Madrid's midfield for a generation. And like a fine wine, he should continue to improve with age.
As Casemiro said afterwards, "Isco is making history at Real Madrid. I hope he will stay here for many years so that we can continue enjoying his magic."