Background Chronic kidney disease (CKD) leads to decreased quality of life (QOL) by increasing the risk of death during the progression of its pathogenesis. However, many factors can be improved to support QOL. This study aimed to assess QOL among CKD patients in Nepal and to determine the factors associated with their QOL. Method A cross-sectional study was used for data collection. CKD cases receiving medical attention in the Bir Hospital in Mahaboudh, Kathmandu; Tribhuvan University Teaching Hospital in Maharajgunj, Kathmandu; Sumeru Hospital in Dhapakhel, Lalitpur; and Shahid Dharma Bhakta National Transplant Centre in Bhaktapur between August and October 2019 were invited to participate in the study. A validated questionnaire and the kidney disease quality of life short form (KDQOL-SF™ 1.3) were used to assess QOL. A questionnaire was completed by the researcher in face-to-face interviews. Logistic regression was used to detect the associations between variables at the significance level of α = 0.05. Results A total of 440 participants were recruited into the study: 56.59% were males, 74.32% were aged between 31 and 70 years, 25.68% were illiterate, and 82.95% were unemployed. The prevalence of good QOL among CKD in the domains of the physical component summary (PCS), mental component summary (MCS), and kidney disease component summary (KDCS) with and without hemodialysis were 53.64, 22.05, 21.28, and 13.19%, respectively. After controlling for all potential confounding factors, eight variables were found to be associated with good QOL in the domain of PCS: age, education, stage of CKD, hemodialysis, transporting oneself to a hospital, health insurance, medical expenses, and perceived lack of difficulty in handling medical expenses. Six variables were associated with good QOL in the domain of MCS after controlling for all potential confounding factors: residence, stage of CKD, transporting oneself to a hospital, health insurance, medical expenses, and perceived lack of difficulty in handling medical expenses. Conclusions Public health interventions should be developed and implemented to improve QOL among CKD patients in Nepal by focusing on older female patients who have low education, live in rural areas and no health insurance.