This study evaluated the relationship between cross-cultural social adaptation and overseas life satisfaction among Chinese medical aid team members (CMATMs) in Africa. A revised Chinese version of the Sociocultural Adaptation Scale (CSCAS) was used to measure participants’ cross-cultural social adaptation. The self-designed survey of the CMATMs’ overseas life satisfaction includes the following five aspects: food, housing, transportation, entertainment, and security. Electronic questionnaires were distributed non-randomly. Linear regression models were established to explore the association between cross-cultural social adaptation and all dimensions of overseas life satisfaction. After adjusting all the confounders, compared with moderate adaptation, poor adaptation was negatively correlated with all dimensions of overseas life satisfaction (B for food = −0.71, B for housing = −0.76, B for transportation = −0.70, B for entertainment = −0.53, B for security = −0.81, B for overall satisfaction = −0.71, all p < 0.001), whereas good adaptation was positively associated with all dimensions of overseas life satisfaction (B for food = 1.23, B for housing = 1.00, B for transportation = 0.84, B for entertainment = 0.84, B for security = 0.76, B for overall life satisfaction = 0.94, all p < 0.001). This study shows that a better cross-cultural social adaptation was positively connected to a higher level of overseas life satisfaction in general, and more specifically to higher levels of satisfaction with food, housing, transportation, entertainment, and security. This knowledge can be utilized in promoting cross-cultural social adaptation and overseas life satisfaction among CMATMs in Africa.