The attacking midfielder featured for 95 minutes, and was instrumental in the game's only goal.
Castellanos' searching corner to the far post was knocked back into the path of Gabriela Garcia, who nodded home from close-range just before the hour mark.
It proved the decisive moment in Caracas, with the City midfielder captaining her nation to a hard-fought victory.
It was Castellanos' first match for Venezuela since a slender 2-1 defeat to Mexico in the Central American and Caribbean Games final in July.
Our number 10 was one of the star performers at the tournament, grabbing stunning goals against El Salvador and Costa Rica en route to winning the Golden Boot.
Castellanos and co. face Uruguay in another friendly next week, locking horns on Tuesday 26 September at 00:00 (UK).
Once again, you can keep across mancity.com and the official Man City app for a report focused on her performance.