The "Culpables" collaborators, who are also dating, reportedly had personal property worth up to $300,000 (£230,000) stolen from their room while on tour in Santiago.
Reports suggest the items swiped included designer luggage, handbags, jewellery, and cash.
Karol G and Anuel AA only discovered the crime when they returned to the hotel following their joint concert at the city's MoviStar Arena.
Local police authorities have since launched an investigation into the robbery.
The news emerges months after Colombian pop star Maluma had a treasure trove of valuables taken from his hotel room while attending the soccer World Cup in Russia last summer (2018), while Daddy Yankee took a hit worth over $2.3 million (£1.8 million) in August (2018) after the safe in his suite was illegally accessed in Spain.