For the rest of the half, Madrid were scatty and imprecise, their finishing spoiled by bad luck but a lack of composure too.
Defeat means Madrid have now gone five games without a victory and by the time Marcelo gave them hope of a comeback at the Santiago Bernabeu, they had gone 481 minutes without a goal too.
Cristiano Ronaldo's hat-trick denied Spain the perfect response to a turbulent week following the sacking of Julen Lopetegui in a thrilling 3-3 draw in Sochi.
Lopetegui has given his backing to Spain at the World Cup, despite being fired as coach just 48 hours before their opening game at the tournament in Russia.
Cristiano Ronaldo's focus is on his fourth and probably last chance to win a World Cup at the peak of his powers.
Hosts Russia got the World Cup off to a flying start by hammering Saudi Arabia 5-0 in the opening game in Moscow.
Spain players reportedly resisted Lopetegui's sacking, which came as Spain are due to face European champions Portugal in Sochi.
Santos is clear in his belief that Portugal will not be caught out by any surprise Spanish tactics following the last-minute upheaval.
Lopetegui was spectacularly axed on Wednesday after it emerged he had agreed to take charge of Real Madrid after the World Cup.
Lopetegui will be officially presented as Real new coach for the next three seasons at an event at the Spanish giants' Santiago Bernabeu stadium at 7 pm (1700 GMT), the club said in a statement.
Untested Spanish coach Fernando Hierro hopes to repeat Zinedine Zidane's coaching success in FIFA World Cup 2018
Hierro is taking on a major coaching job without any significant previous experience, just as Zidane did at Real Madrid.
The 33-year-old will lock horns with six of his Real Madrid team-mates as the Spaniards try to repeat 2010.
Lopetegui never lost in 20 games as Spain boss, but even in a flawless qualifying campaign on the field, the Madrid-Barca rivalry.
The 50-year-old Hierro's only real coaching experience came when he was in charge of second division Spanish outfit Oviedo for one season.
Real Madrid named Lopetegui as their next manager to start work after the tournament in Russia, sparking outrage among the federation and Spanish fans.