Research considering physical activity (PA), physical inactivity and health outcomes among urban and rural youth has produced equivocal findings. This study examined PA, physical inactivity, sedentary behaviours and cardiorespiratory fitness (CRF) in adolescents from urban and rural communities in the Portuguese Midlands. The sample included 362 adolescents (165 males, 197 females) of 13–16 years of age. CRF was assessed by the PACER test. A GT1M accelerometer was used to record 5 consecutive days of PA and time spent sedentary. Analyses of covariance (chronological age as co-variate) were performed to test the effect of the area of residence on sedentary behaviour, PA and CRF. Urban youth of both sexes spent less time in sedentary activities than rural youth. Urban males were more active than rural peers at the weekend, whereas urban females were significantly less active than rural females on week days and across all days assessed. Rural youth of both sexes had higher levels of CRF than urban youth. Area of residence was related to aerobic fitness, PA and time spent in sedentary behaviours among Portuguese youth. Interventions seeking to enhance health and active lifestyles in Portuguese youth should consider the potential impact of socio-geographic factors.