Background Maternal mortality remains a major challenge to health systems in low and middle-incoming countries. Some pregnant women develop potentially life-threatening complications during childbirth. Therefore, home delivery is a precursor for maternal mortality. In this study, we aimed at not only estimating the percentage of deliveries occurring at home and examining the factors associated with home delivery, but we also explored the reasons for home delivery among women in rural Ghana. Methods The study was conducted among mothers with delivery experience in selected communities in the Builsa South district located in the Upper East Region of Ghana. Both quantitative and qualitative data were collected using semi-structured questionnaires and Focus Group Discussion (FGD) guide respectively. A total of 456 mothers participated in this study. Regression models were used in the quantitative analysis whereas a thematic analysis approach was used to analyze the qualitative data. Results Of the 423 mothers in the quantitative research, 38.1% (95% CI: 33.5-42.8) delivered their index child at home. In adjusted analysis, women who were not exposed to information (AOR = 13.64, p<0.001) and women with 2 (AOR = 4.64, p = 0.014), 3 (AOR = 4.96, p = 0.025) or at least 4 living children (AOR = 9.59, p = 0.001) had higher odds of delivering at home. From the qualitative analysis, the poor attitude of nurses (midwives), lack of, and cost