Self-injection of DMPA-SC method is one of the Government of Nigeria’s (GON) national family planning goals to address the unmet need for contraception. Some studies on DMPA-SC/SI have demonstrated its feasibility to improve modern contraceptive uptake. However, there is a gap in the predictors of method uptake and continuation across self-injecting and provider-administered in Nigeria. This study explored the uptake of self-injection DMPA-SC contraceptives among women in two geopolitical zones of Nigeria. The study employed 20 focused group discussions (FGDs) and 40 In-depth interviews (IDIs). Self-structured pretested questionnaire to elicit information from 844 women registered for Family Planning in selected health facilities. Descriptive statistics were calculated, and multivariate logistic regression was used to model determinants of DMPA-SC/SI family planning uptake. Six months of Secondary Data from the Health Management Information system (HMIS) was used to triangulate the trends in uptake. About 97.6% reported ever heard DMPA-SC/SI family planning method; 78.4% reported its uptake, while 88.5% reported ever heard of self-injection as an option of family planning method. Data for each State showed a remarkable increase in uptake of DMPA-SC/SI. The motivations to use DMPA-SC/Self Injection were ease of accessibility, convenience, and self-administer/care. Factors that encourage the uptake of DMPA SC/SI were; health benefits, the prevailing economic situation and its effectiveness. Findings from the study showed that interventions that deploy health education, awareness, social mobilization, advocacy, policy implementation, and public sensitization, making contraceptive services available for free, will increase the uptake of DMPA-SC/SI in the study areas.