The two European giants remain locked on 16 points at the top of Group G of UEFA qualifying after Italy saw off Liechtenstein 5-0 in Udine.
However, Spain have a superior goal difference and host the Azzurri in their next qualifier at Real Madrid's Santiago Bernabeu on September 2.
Only the group winners automatically book their place in Russia with second place left to fight out a two-legged playoff in November.
"It is going to be the most important game of the group," Isco told Spanish TV station Teledeporte.
"But we are at home, we hope the Bernabeu will be a fortress and, at the end of the day, it is in our hands."
Victory extends Julen Lopetegui's unbeaten record as Spain boss since replacing Vicente del Bosque just under a year ago, and the visitors looked to be set for an easy night in Skopje after a dominant first 45 minutes.
"We have achieved our objective which was the three points in a difficult game for the time of year," said Lopetegui.
"Other than the goal, we didn't suffer, but it is true that just a one goal difference made us struggle more than expected after seeing the first-half."
Silva has been the talisman of Lopetegui's reign and took his tally to eight goals in his last 10 international caps by finishing off a fine move involving Andres Iniesta and Jordi Alba for the opener on 15 minutes.
Isco was rewarded for his brilliant form towards the end of Real's La Liga and Champions League double-winning campaign with a rare start for his country and looked keen to make an impact.
He stung the palms of Stole Dimitrievski before driving another effort just over the bar.
There was no stopping Isco midway through the half, though, as some sublime skill took him past Kire Ristevski before his low cross was turned home by Costa at the back post.
"I ended the season very strongly and for any player it is important to have the confidence of the coach," added Isco.
"They were three important points against opponents that made things difficult for us and now it is time to rest."
Isco should have added a third before half-time when he dallied before firing too close to Dimitrievski at his near post.
However, Spain looked like a side in need of a rest after a long season as they took their foot well off the gas after the break to allow Macedonia back into the game.
It took an individual moment of brilliance from Stefan Ristovski to give the hosts hope, though, as the right-back charged forward before blasting high into David de Gea's top left-hand corner.
Dimitrievski was forced into one last save four minutes from time to prevent Costa adding a gloss to the scoreline, but Lopetegui's men comfortably saw out the final stages for a hard-earned three points.