(1) Background: Universities play a crucial role in nurturing healthy habits, and physical activity has emerged as a valuable tool for enhancing the life satisfaction, self-efficacy, and resilience of college students. Therefore, the purpose of this study was to investigate the mediating role of physical activity in the relationship between life satisfaction and self-efficacy as well as resilience among Chinese university students. (2) Method: This study used the Physical Activity Rating Scale (PARS-3), the Self-Efficacy Scale (CGES), the Mental Toughness Scale (CD-RISC), and the Life Satisfaction Scale (CSLSS) to administer questionnaires to 353 university students from two universities in Chengdu, Sichuan Province. Using a random simple sampling method, the data were processed and analyzed using SPSS 22.0 and Excel software. (3) Results: (1) Physical activity exhibited a significant positive correlation with self-efficacy, resilience, and life satisfaction; self-efficacy was significantly and positively related to resilience and life satisfaction; and resilience was significantly and positively related to life satisfaction. (2) Physical activity had a positive predictive effect on life satisfaction (β = 0.2771; 95% confidence interval (CI): 0.1905, 0.3637, 55.51%). (3) Self-efficacy (β = 0.0368; 95% confidence interval (CI): 0.0087, 0.0692, 7.37%) and resilience (β = 0.137; 95% confidence interval (CI): 0.0919, 0.1894, 27.44%) mediated the relationship between physical activity and life satisfaction. Also, the chain-mediating effect of self-efficacy and resilience between physical activity and life satisfaction reached significant levels (β = 0.0483; 95% confidence interval (CI): 0.0279, 0.0745, 9.68%). (4) Conclusion: Active participation in physical activity not only enhanced the life satisfaction of college students but also indirectly impacted their life satisfaction by improving their self-efficacy and resilience. Consequently, this led to an overall improvement in the life satisfaction of college students.