Luis Enrique took charge after the humiliating exit to Russian Federation at the World Cup had left Spain doubting the possession game that won them three consecutive major tournaments between 2008 and 2012.
It was the biggest defeat ever for Croatia, which was playing its first competitive game since reaching the World Cup final in Russian Federation.
Croatia suffered the biggest defeat in their history as Spain thrashed them 6-0 in Tuesday's Nations League match at Estadio Manuel Martinez Valero.
The result is their heaviest ever defeat, the first time they have conceded six goals and the first game in which they have let in five since a 5-1 loss to England in 2009.
The two teams last met at Euro 2016 when Croatia came away with a 2-1 win after overturning Spain's lead. During the Russia World Cup, they were the most represented club with six players.
The UEFA Nation's League match between Spain and Croatia will be broadcast live on ESPN2 and Univision Deportes.
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Marco Asensio was their outstanding performer with one goal - Spain's second, driven in from 25 yards - and three assists.
Rodrigo scored after slipping past the Croatian backline on a through-ball from Asensio in the 49th minute.
He promised evolution, not revolution, and while his team still dominated possession, they were faster, more direct and less predictable in the final third.
Isco capped Spain's offensive show with a right-footed shot from the center of the box in the 70th minute.
Croatia will hope to get their first Nations League points when they host England next month. Three superbly weighted deliveries of different styles gifted his side further goals in the second half and underlined his remarkable quality. In the 57th minute, Spain captain Sergio Ramos headed in his 14th worldwide goal for the team's fifth on the night.
Spain have now won both of their opening UEFA Nations League games and on this evidence will take some stopping in League A.
"Croatia are the World Cup runners-up and all teams will be motivated against us - and we have to be aware of that".