Background: The detection of cancer in its early latent stages can improve patients’ chances of recovery and thereby reduce the overall burden of the disease. Our objectives were to investigate factors (geographic accessibility and deprivation level) affecting mammography screening participation variation and to determine how much geographic variation in participation rates can be explained by spillover effects between adjacent areas, while controlling for covariates. Methods: Mammography screening participation rates between 2015 and 2016 were calculated by census blocks (CB), for women aged 50–74 years, residing in Lyon metropolitan area. Global spatial autocorrelation tests were applied to identify the geographic variation of participation. Spatial regression models were used to incorporate spatial structure to estimate associations between mammography participation rate and the combined effect (geographic accessibility and deprivation level) adjusting for modes of travel and social cohesion. Results: The mammography participation rate was found to have a statistically significant and positive spatial correlation. The participation rate of one CB was significantly and positively associated with the participation rates of neighbouring CB. The participation was 53.2% in residential and rural areas and 46.6% in urban areas, p < 0.001. Using Spatial Lag models, whereas the population living in most deprived CBs have statistically significantly lower mammography participation rates than lower deprived ones, significant interaction demonstrates that the relation differs according to the degree of urbanization. Conclusions: This study makes an important methodological contribution in measuring geographical access and understanding better the combined effect of deprivation and the degree of urbanization on mammography participation and other contextual factors that affect the decision of using mammography screening services -which is a critical component of healthcare planning and equity.