University represents a critical transition from secondary school. University students are exposed to many new opportunities and intellectual stimulations, and some may find university life stressful and demanding. The quality of life (QoL) of university students is thus an important topic for researchers and educators alike. Furthermore, many universities are now paying attention to the spirituality of students, besides emphasizing their cognitive and psychosocial development. Using a sample of 1,160 Chinese university students mainly recruited from Hong Kong, this autoregressive cross-lagged panel study investigated a causal model of spirituality and QoL over a 3-year period. The study also tested the causal model for factorial invariance (configural, measurement, and structural invariance) across gender, religion, and time. Results indicated that spirituality was a causal predictor of QoL but not vice versa. There was some evidence to support factorial invariance of the model across gender, religion, and time. The theoretical and practical implications of the findings are discussed.