The concern for this study is to show and prove how human population is a vital issue in development plan. It is a strong determinant of the socio-economic and political prosperity of a nation. However, rapid population growth in the absence of commensurate material and financial resources could constitute a significant problem in society; consequently, factors that influence regional population growth is of great importance to policy makers, researchers and students. This study examines the socio-cultural and economic determinants of fertility differentials in rural and urban south-west Nigeria with specific focus on Lagos and Ile-Ife communities. Survey design was adopted and a sample of 6766 respondents was drawn with the use of Nigeria Demographic and Health Survey (NDHS). The study elicited data via structure questionnaire and focus group discussions (FGD). Hypotheses of the study were tested using bi-variate and multi-variate techniques. Findings revealed that age at entry into marital union, contraceptive use and educational level significantly determined fertility differentials between rural and urban communities in South-Western Nigeria.