City's number 10 made an impact as a second half substitute in Caracas, putting her nation ahead with a clinical finish just after the hour mark.
Castellanos latched onto a long ball over the Uruguay defence, clipping the ball back onto her right foot and away from a retreating defender before rounding the onrushing goalkeeper and finishing into an empty net.
It was a typically classy goal from the Venezuelan who has made a habit of finding the net in spectacular fashion, including several en route to finishing as top scorer at this summer's Central American and Caribbean Games.
This was the second occasion that Castellanos and co. had faced Uruguay in this international break, having also locked horns in Caracas four days earlier.
Venezuela came out on top by a single goal on that occasion as well, with the City attacking midfielder's deep corner crucial in the build-up to the game's decisive moment.
A number of Castellanos' City team-mates could be in action this evening in the latest round of UEFA Women's Nations League fixtures.
Keep across mancity.com and the official Man City app this evening for a City-focused roundup on those fixtures.
RISE: The Story of our Season
‘Rise: The Story of our Season’ – the latest documentary from City Studios - will be released on CITY+ this Friday, charting the progress of Manchester City Women across the 2022/23 campaign.
Records were broken, reputations were forged, and an exciting young squad showed they could go toe-to-toe with the best that England has to offer.
Our cameras were there every step of the way, capturing the thrills and spills of a compelling WSL title race which went down to the wire.
With candid reflections from players and coaches alike, ‘Rise’ provides a window into the personalities behind the stars you’ve seen on the pitch, while also nodding towards what should be another enthralling campaign, which begins on Sunday against West Ham United.
Keep across mancity.com, the official Man City app and our social platforms across this week for teaser clips from the documentary.
For more information on subscribing to CITY+, click here.