Valbuena was 33 and Castillo was 37.
The crash occurred after Valbuena and Castillo left the University Stadium at Caracas after playing a game in the Venezuelan Professional Baseball League. Venezuelan authorities said their car went to the opposite side of the road while trying to avoid a sliding rock.
The players were en route to the city of Barquisimeto, where they were planning to play against Bravos de Margarita on Friday.
Valbuena played 11 seasons in the majors, including his final two with the Los Angeles Angels, who released him in August. He also played with the Seattle Mariners, Cleveland Indians, Chicago Cubs, and Houston Astros.
Castillo played in the majors from 2004 to 2008, with the Pittsburgh Pirates, San Francisco Giants and Astros.
We send our deepest condolences to the family and loved ones of former Mariner Luis Valbuena.— Seattle Mariners (@Mariners) December 7, 2018
He played the game with passion and he will be missed. pic.twitter.com/EhTNeSP5OM
We are deeply saddened to hear of the passing of former Angel Luis Valbuena and former MLB infielder José Castillo. Our thoughts and prayers are with their loved ones during this time of grief. pic.twitter.com/GxegOtJXuB— Angels (@Angels) December 7, 2018