The 6-0 scoreline was Croatia's biggest-ever defeat.
Three goals in the space of 11 first-half minutes put the hosts on their way to a second successive UEFA Nations League victory, and they were five up before the hour mark.
More importantly, they are off to a winning start under Luis Enrique, with their performances in Elche and against England at Wembley a stark reminder of the quality they possess, which seemed to go missing in their tempestuous World Cup campaign.
The two nations are facing each other for the seventh time, with Croatia taking the last meeting - a 2-1 win at Euro 2016.
Spain have now won both of their opening UEFA Nations League games and on this evidence will take some stopping in League A.More news: Tesla shares fall after Elon Musk smokes weed, drinks whisky during interview
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Ten minutes later Marco Asensio made it 2-nil with a powerful shot.
La Roja were surely out of sight four minutes after the break as Rodrigo made it 4-0 with a strike from the right side of the box into the bottom corner following a through ball from Asensio.
Spain manager Luis Enrique has rubbished suggestions that only one Barcelona player started in their UEFA Nations League match against Croatia exclusively because of hard feelings towards his former employers.
Croatia will hope to get their first Nations League points when they host England next month. They are not from one team or another. During the Russia World Cup, they were the most represented club with six players. The former Barcelona coach also added defender Jose Luis Gaya and midfielder Dani Ceballos to the starting lineup.
Just like it did against England, Spain was aggressive without the ball on Tuesday, pressing high and playing a more direct game that takes the focus away from short passes, something that has become a characteristic of Enrique's team.
Belgium had defeated Scotland 4-0 in a friendly last week in Glasgow.