Goals from Alvaro Morata and Nolito saw the holders take a two-goal lead into the break, before Morata scored his second early in the second period to make it a comfortable night for Vicente del Bosque's side, who have become the first team in this summer's tournament to score three times in a group match.
Spain captain Sergio Ramos picked up a booking inside the first minute and that challenge set the tempo as both teams battled for early control of the possession in Nice.
The game's first attempt on target came in the sixth minute when Morata spun outside the Turkish box and sent a low strike towards the bottom corner, but Volkan Babacan was on hand to make a smart save.
In the 11th minute, Spain again came close when Jordi Alba delivered a low cross towards the near post, but Turkish full-back Hakan Balta managed to turn against his own post under pressure from Morata. Gerard Pique met the resulting corner, but his header hit the ground and bounced over the target.
Calhanoglu then had an opportunity to threaten the Spain goal from a free kick some 30 yards from goal, but once again the 22-year-old sent his effort over the crossbar as it remained all square with 27 minutes on the clock.
Nolito showed excellent feet down the left to cut inside and release a curling strike towards the bottom corner as Spain came close to making the breakthrough, but the attacker's effort just missed the target.
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Spain did take the lead in the 34th minute, however, when Nolito delivered a cross onto the head of Morata, who simply guided the ball into the far corner with a clever flick.
Three minutes later, Spain doubled their lead as Nolito, having made the opener, got his name on the scoresheet. A pass from Fabregas put Turkish centre-back Mehmet Topal under pressure and the number 15 could only head into the space where Nolito was lurking and the attacker placed his effort into the corner of the net.
Spain continued to break forward in the latter stages of the first period and came close to a third when Morata broke away and fed a low cross into Pique, but Topal just about managed to clear at the vital moment.
Spain started the second period as they finished the first and they scored a third in the 48th minute when Iniesta delivered a low pass into Alba and the left-back squared for Morata, who tapped home from close range.
Burak Yilmaz should have scored for Turkey in the 52nd minute after turning Pique inside the Spain box, but the striker, who entered the match on 20 international goals, got his effort all wrong and it flew wide of the post.
David Silva had two opportunities to score a fourth for Spain either side of the hour, but the Manchester City attacker just missed the target on both occasions as it remained 3-0 entering the final 30 minutes.
Bruno Soriano was introduced in the 64th minute and came close to scoring five minutes after entering the pitch, but the Villarreal midfielder's strike from distance was pushed wide of the post by Babacan.
The atmosphere turned sour in the latter stages when the Turkish supporters booed their captain Arda Turan following another disappointing performance and Spain's game management kicked in as they controlled the possession.
Turkey were given licence to break forward as Spain looked to keep their clean sheet intact, but it was an extremely comfortable night for new number one De Gea in the La Roja net.
Spain will take on Croatia on Tuesday for the right to finish top of the group, while Turkey will attempt to secure a top-three finish when they face Czech Republic on the same night.