Objective: Assess quality of life and mental health implications of mastectomy for breast cancer on sub-Saharan African women. Background: Mortality rates amongst women diagnosed with breast cancer in sub-Saharan Africa (SSA) are high, with disparities in survival relative to women in high income countries partly attributed to advanced disease at presentation. Fears of the sequelae of mastectomy are a prominent reason for presentation delays. There is a critical need to better understand the effects of mastectomy on women in SSA to inform preoperative counseling and education for women with breast cancer. Methods: Women with breast cancer in Ghana and Ethiopia undergoing mastectomy were followed prospectively. Breast related quality-of-life and mental health measures were evaluated preoperatively, 3 and 6 months postoperatively, using BREAST-Q, PHQ-9, and GAD-7. Bivariate and logistic regression analyses evaluated changes in these measures for the total cohort and between sites. Results: A total of 133 women from Ghana and Ethiopia were recruited. The majority of women presented with unilateral disease (99%) and underwent unilateral mastectomy (98%) with axillary lymph node dissection. Radiation was more common in Ghana (P < 0.001). Across most BREAST-Q subscales, women from both countries reported significantly decreased scores at 3 months postoperative. At 6 months, the combined cohort reported decreased scores for breast satisfaction (mean difference, -3.4). Women in both countries reported similar improvements in anxiety and depression scores postoperatively. Conclusions: Women from Ghana and Ethiopia who underwent mastectomy experienced a decline in breast-related body image while also experiencing decreased levels of depression and anxiety.