This study examined obesity inequalities according to place of birth and educational attainment in men and in women in Spain. A cross-sectional study was conducted using data from the Spanish National Health Survey 2011–2012 and from the European Health Survey in Spain 2014. We used data for 27,720 adults aged 18–64 years of whom 2431 were immigrants. We used log-binomial regression to quantify the association of place of birth with obesity before and after adjusting for the selected characteristics in women and in men. We found a greater probability of obesity in immigrant women (PR: 1.42; 95% CI: 1.22–1.64) and a lower probability of obesity in immigrant men (PR: 0.73; 95% CI: 0.59–0.89) relative to natives after adjustment. Significant heterogeneity was observed for the association of place of birth and obesity according to education in men (p-interactions = 0.002): Men with lower educational levels (PR: 0.47; 95% CI: 0.26–0.83) have a protective effect against obesity compared with their native counterparts. This study suggests that place of birth may affect obesity in women and in men. However, this effect may be compounded with education differently for women and men.