Background Biological fathering, especially in patrilineal societies, was traditionally acceptable only in the context of marriage to the mother of the child. Many men were polygynous, often staying in one household with all their wives and children. However, this phenomenon has been on the decline in recent times, mainly due to Christianity, which encourages monogamy while frowning on polygyny. The Ghanaian family has for the past few years been undergoing changes due to migration, urbanization, and industrialization. With an increase in non-marital births and the dissolution of marital unions, multi-partner fertility is likely to increase. Contemporary Ghanaian perspectives on the circumstances that lead men to engage in paternal multi-partner fertility, otherwise referred to in this study as serial fathering, are scanty, hence this study examines the factors that lead to serial fathering among Ghanaian men. Methods The study employed the qualitative method, using in-depth interviews with twenty (20) serial fathers and a focus group discussion with seven (7) women. Results It was found that factors such as the attitude of women in relationships, the duolocal post-marital residential pattern, and the age at first birth are some of the reasons why some men father children with multiple partners. Conclusion The study concludes that both situational and personal factors account for the phenomenon of serial fathering amongst men in Prampram, Ghana, and these factors bring about distinctions in serial fathering as occurring either within or outside of marriage.