Introduction: Mastectomy is a treatment option for patients diagnosed with breast cancer. There is very limited research into the psychosocial impact of mastectomy on female breast cancer patients, especially in the sub-Saharan African setting which has unique cultural norms. The study aimed at assessing the psychosocial impact of mastectomy on female breast cancer patients attending a radiotherapy/oncology centre in Ghana. Methods: A cross-sectional design was used to undertake this study. A total of 80 female mastectomy breast cancer patients participated in this study. A semi-structured questionnaire was used for data collection over a 5-month period, January to May 2018. The data collected were analysed with Statistical Package for Social Science (SPSS) version 22. Results: Most of the participants were adversely affected psychologically and emotionally by mastectomy. In particular, many (56·7%) agreed that they felt less feminine, and 71% reported they experienced psychological distress as a result of their mastectomy, while 63% of them reported loss of self-confidence. A large proportion of them (51, 63·8%) agreed that their lifestyles had changed following mastectomy, while 58% of them admitted that they felt treated as outcasts by society, and 75% resorted to the use of breast prostheses to reduce attention. Conclusion: The study revealed that mastectomy for breast cancer patients had a negative impact on their psychological, emotional and social well-being. The availability of affordable breast prostheses, involvement of clinical psychologists in the care of post-mastectomy women, provision of emotional, psychological and even financial support could alleviate the psychosocial impact of affected women.