Background: There is little known about physical activity (PA) behaviors and its determinants in Cambodian adolescents, particularly with regard to the home and school settings. Therefore, we aimed to investigate these behaviors and determinants on their PA. Methods: The samples collected were from 168 high school students, aged 14–15 years. They were requested to complete the self-report PA questionnaire. Time spent in PA during weekday and weekend by school location and gender, and determinants on PA were analyzed. Differences in the mean values of the PA levels (in minutes) during weekday and the weekend between genders, and between school locations were analyzed using independent sample t tests. The percentage of students’ perceptions on the determinants were calculated. Chi-squared test was used to compare the differences in prevalence of students’ activities during their free time with respect to school location and gender. Results: The majority of the parents (86.9%–98.2%) demonstrated strong support for their children for academic work. Rural students spent an average time of moderate-to-vigorous PA greater than their counterparts from the urban areas during their weekend days (329.1 vs 239.2 min, respectively). Moderate to vigorous PA was likely to be higher during the weekends compared with weekdays among the boys (387.9 vs 361.4 min, respectively). Girls were more likely to spend their time on moderate to vigorous PA during the weekdays compared with the weekends (205.4 vs 180.5 min, respectively). Conclusion: Consideration should be given to gender, school location, free time, and the environmental setting for the contextualization of more effective PA interventions with Cambodian youths.