Psychosocial factors such as mental health, motivation, and social support are key determinants of behavior that play a significant role in physical activity participation. Limited studies have investigated the relationship between psychosocial factors and physical activity among university students in Africa. The aim of this study was to determine the relationship between psychosocial factors and physical activity participation among undergraduate university students at a historically disadvantaged university (HDU) in South Africa. This was a cross-sectional study that used convenience sampling ( = 534, majority female, 53.6% with a mean age of 20.69). The study was conducted through an online, self-administered, and hard-copy, valid questionnaire in September 2022. Data on sociodemographic information were collected. Psychosocial factors were assessed using the Depression, Anxiety, and Stress-21 Scale for mental health, the Physical Activity and Leisure Motivation Scale for motivation, and the Perceived Social Support Scale for social support. Physical activity (calculated as MET-min/week) was assessed using the international physical activity questionnaire in short form. Results revealed that almost a third (29%) of undergraduate students were physically inactive, 31.1% were minimally active, and 39.9% were in the health-enhancing category. Physical activity was positively related to stress (r = 0.11, < 0.05) and anxiety (r = 0.10, < 0.05). Motivational factors were positively related to psychological condition and others' expectations (r = 0.10, < 0.05), and depression and others' expectations (r = 0.11, < 0.05). Results from this study highlighted that psychosocial factors were related to physical activity participation among undergraduate university students. Psychosocial factors should be considered a coping mechanism when implementing health-promoting strategies.