Ana Lelas, who is enjoying an outstanding season with Bourges in the EuroLeague Women, led six players in double figures with 23 points for the winners.
The Croatians, entering this phase of the competition after just two victories in their eight games last year in Division A, reeled off the first five points of the contest and stayed in front the rest of the way.
With 3:42 still remaining in the first quarter, Ivana Jurcevic buried a shot from the arc for a 22-12 lead and took her points haul to nine.
Lelas followed with another three for a 25-12 advantage.
By the end of the opening frame, Croatia had a 34-15 stranglehold on proceedings
Belgium twice closed the gap to 10 points in the second quarter but got no closer.
Sara Leemans had a game-high 29 points for Belgium, who were 2-4 in Division A last year.
The visitors were out-rebounded 42-27.
Stipe Bralic (coach Croatia):
"I am satisfied with the match. Even though we had only a few days to practice, we played well. There are still some things to be changed, especially in defense. Our defensive play has to be improved before the match in Italy."