Practising active video games (AVGs) requires performing motor and cognitive tasks, which might foster success in physical education and other school subjects but remains poorly investigated. This study examined the learning effects of six lessons using AVGs with physical education and mathematics content. Overall, 216 school-students composed an experimental group (n = 99) and a control group (n = 107). Both attended six lessons, each on using a Cartesian coordinate system and ball-throwing accurately, with AVGs in the experimental group only. Learning was assessed at Lessons 1 and 6, situational interest and moderate-to-vigorous physical activity (MVPA) at Lessons 3 and 5. MANOVAs showed no between-group differences in situational interest and higher MVPA for the control group at Lesson 3 only. Statistical analysis showed higher learning scores (mathematics and physical education) for the experimental group at Lesson 6, suggesting possible interest in AVGs during multidisciplinary sequences connecting physical education and mathematics.