The game's opener came from Croatian frontman Duje Cop, before Isco equalised three minutes later with an excellent solo effort.
Winning in Madrid is no easy task and even a 1-0 victory on Tuesday will not be enough after a 2-1 first-leg, quarterfinal loss in Munich.
Isco popped up again in the final minute of normal time to seal the victory and cap a fraught 90 minutes for Real, who are now six points clear of Barcelona in second, ahead of next weekend's crucial El Clasico.
The 24-year-old is one of a number of talented players who have had to make do with life on the fringes at the Bernabeu this season, and it would be no surprise to see him move on this summer in search of more first team football.
As if the Real Madrid midfielder's early equaliser against Sporting Gijon wasn't good enough, Isco went on to seal the victory with a dramatic injury time victor.
Isco showcased his dribbling skills in the 71st minute when he picked the ball at the centre-line and swirled through the Gijon defence, flooring the defenders on the way before Jorge Meré's defensive attempt prevented him from making an attempt on the goal.
Real Madrid have scored 18 goals after the 80th minute in #LaLiga this season; more than any other club.
This led to Tottenham fans on social media paying special attention to the display of the 20-time capped Spain global at the weekend and many were impressed.
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Vesga then again put Sporting in the lead with a looping header before in the second half Alvaro Morata levelled with his head in the 59th minute.
The eccentric former Arsenal captain didn't disappoint in his first press conference where he promised to "kick some players' arse" in an uphill battle to save Granada from relegation in the final seven games of the season.
"It'll be a great game", said Bayern coach Carlo Ancelotti, who led Madrid to the 2014 title.
- Real Madrid are the side in the top five European Leagues with the most headed goals scored this season (25).
Mariano failed to find the target with his 81st minute header from a good Rodriguez delivery but Real were to finally find the goal their play deserved, as Isco swept home at the near post from the left hand side after a pass forward from substitute Marcelo.
"Technically, Isco is a lot like me", Real Madrid manager Zinedine Zidane had said about the Spanish midfielder in 2015, when he was managing Real Madrid's youth side - Real Madrid Castilla. "We need everyone and everyone responds".
Future: "I'm in the best team in the world, there is no club bigger than Real Madrid and I feel very fortunate to be here". "It was a relief to score at the end and take the three points".