The 33-year-old Valbuena and 37-year-old Castillo died late Thursday when their SUV crashed as it tried to veer around an object on the road, Yaracuy state Gov. Julio Leon Heredia said on his Twitter account. Officials said some bandits place or throw objects on highways to force vehicles to stop or crash so they can rob the occupants.
Heredia said four people have been detained after being found with property of the athletes.
Valbuena and Castillo were teammates on the Cardenales de Lara team in the Venezuelan winter league and were returning from a game in the capital when the crash occurred en route to the city of Barquisimeto.
Third baseman Carlos Rivero was in the car and survived, according to the website beisbolplay.
Valbuena, an 11-year major league veteran, recently played for the Los Angeles Angels and had been a free agent since the end of the 2018 season. Valbuena played three seasons for the Cubs from 2012-2014, playing in 347 games for the Cubs, hitting 32 home runs and 116 RBI.
In a statement on Twitter, the Cubs said, "We are saddened by the passing of former Cub Luis Valbuena. The #Cubs organization sends its condolences to his family and friends."
Castillo played for the Pittsburgh Pirates, San Francisco Giants and the Houston Astros between 2004 and 2008.
"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," the Angels said in a statement.
We are saddened by the tragic news that Luis Valbuena and former major leaguer José Castillo have died in a car accident. pic.twitter.com/C3nILO00SE— MLB (@MLB) December 7, 2018
"I will miss Luis' banter, smile, genuine love for his teammates, and, of course, the bat flips," Astros manager AJ Hinch said in a statement. "He was a beloved person whether he was on our team or across the field."
"Luis was always smiling and was one of the happiest players in baseball," Astros general manager Jeff Luhnow said in a statement. "He provided joy to his teammates and our fans. He helped our franchise turn a corner in 2015 and provided many cherished memories."
Castillo played five seasons with Pittsburgh, San Francisco and Houston. He had a .254 average with 39 home runs.
Venezuelan President Nicolas Maduro said in a tweet that "I join in the mourning that has overwhelmed the Venezuelan baseball family and all of its fans."
Baseball Commissioner Rob Manfred issued a statement calling it "a very sad day for our sport."
Celebrities and notable figures who have recently passed away
"It is clear by all the stories today that they loved baseball and made an impact on their teammates and the Clubs they represented," he said, expressing "my deepest condolences to their families, friends and fans, particularly those in their native Venezuela."
By late Friday afternoon, the coffins with the players' bodies had arrived in Antonio Herrera Gutierrez stadium in Barquisimeto where they were received amid tears by their teammates. A Mass was held to bid them good bye.
The Venezuelan Professional Baseball League announced that all three scheduled games Friday were cancelled and it said flags will fly at half-staff in all stadiums for three days.
League president Juan Jose Avila told Union Radio that he was evaluating the possibility of forbidding players from traveling in private cars to move between games, saying if the players had been on the team bus, "nothing would have happened to them."
Venezuelan teams tend to travel in buses protected by security forces.
WLS-TV contributed to this report