Smartphone use among college students is prevalent across the world. Recently, research has begun to investigate the relationship between smartphone use and physical activity. This study examined the amount of time spent using a smartphone and the physical activity (PA) levels among college students majoring in health science-related disciplines in the United States (US) and Thailand. Using convenience sampling, college students in the US (n = 242) and Thailand (n = 194) completed an online survey, in Fall 2016, assessing smartphone usage and PA. Data were analyzed using chi-square tests and two-way ANOVA (p < 0.05). US students reported more days per week ( U = 15,150.0 , p = 0.00 , r = 0.33 ) and greater duration of PA ( U = 11,234.0 , p = 0.00 , r = 0.33 ) than Thai students while Thai students used smartphones more per day than US students ( U = 13,137.5 , p = 0.00 , r = 0.40 ). No difference existed for years of smartphone use ( U = 22,207.0 , p = 0.27 ). Greater smartphone use per day inversely related to days per week of engaging in PA among Thai students ( X 2 ( 3 ) = 10.55 , p = 0.01 , ε 2 = 0.06 ), but not among US students ( X 2 ( 3 ) = 2.39 , p = 0.50 ). The high smartphone use among college students, especially in Thailand, may be a barrier to PA as well as a strategy for PA promotion in higher education settings. Research should examine the best techniques for smartphone application development to promote PA in college settings.