Background It is generally accepted that pregnancy and childbirth are natural physiological processes. However, these significantly affect the quality of mothers’ lives. Little is known about the level of quality-of-life and associated factors among postpartum women in Ethiopia, particularly in the study area. Methods A community-based cross-sectional study was conducted among 409 randomly selected post-partum women who were living in Arba Minch town. Systematic random sampling was employed to select the study participants. The standard quality-of-life assessment tool which is known as the short-form SF 36 tool was used to assess health-related quality-of-life. The logistic regression model was used to identify associated factors. Statistically significant variables at a p -value<0.25 in the bi-variable analysis were candidate variables for multi-variable analysis and statistical significance which was declared at a p -value<0.05. Results Among the study participants, 255 (62.3%) had lower level health-related quality-of-life (HRQoL). About 46.2% of the study participants had lower physical HRQoL and about 79% of the study participants had lower mental HRQoL. The overall mean score of HRQoL was 45.15 (±8.13). Factors associated with lower overall HRQoL were age group 17–24 years (AOR=2.73, 95% CI=1.22–6.10), no formal education [AOR 2.02, 95% CI (1.05–3.89)], and cesarean delivery (AOR=0.49, 95% CI=0.24–0.97). A factor associated with lower physical HRQoL was cesarean delivery (AOR=0.34, 95% CI=0.13–0.88). Factors associated with lower mental HRQoL were age group 17–24 (AOR=3.37, 95% CI=1.60–7.04), not receiving antenatal care (AOR=3.65, 95% CI=1.45–9.16), and having postpartum depression (AOR=2.27, 95% CI=1.30–3.93). Conclusion The results suggest that the majority of post-partum women had a lower HRQoL, particularly women’s mental health was compromised. In this study, a suggestion is made that the respective bodies need to give particular attention to mothers during the post-partum period to prevent poor quality-of-life.