Background Research has increased our understanding of the parental factors associated with the initiation and development of cannabis use disorder in adolescents, but few studies about this have been performed in middle- or low-income countries. Objective First, to examine whether perceived past parental drug use, parental monitoring, and attitude toward adolescent cannabis use are associated with general and problematic cannabis use in Chilean adolescents. Second, to explore whether perceived past parental drug use weakens the associations of protective factors with general and problematic adolescent cannabis use. Methods Regression analyses were performed on cross-sectional data from a multistage probabilistic sample stratified by clusters (municipalities, school and grade) of 43,060 students (47% male, mean age 15.5 years) from grades 8 to 12, which was collected from the Chilean National School Survey on Drug Use (2013). Results Perceived past parental drug use increased the likelihood of adolescent cannabis use in general, but not its problematic use. Parental monitoring of adolescents' whereabouts and parental opposition to adolescent cannabis use decreased the likelihood of adolescent cannabis use in general, as well as problematic use. Perceived past parental drug use only interacted with parental monitoring of school activities. Conclusions In line with research from the United States, the Netherlands and Spain, parental monitoring of adolescents' whereabouts and a strong parental opposition to cannabis use appear to be protective factors, irrespective of past parental use. However, the effectiveness of monitoring adolescents' school activities seems to decrease when parents are perceived as having used drugs in the past.