Despite the global emphasis on breastfeeding, exclusive breastfeeding (EBF) in the first six months of life still lag behind the global recommendations in low- and middle-income countries, such as Nepal. This systematic review aims to determine the prevalence of EBF in the first six months of life and the associated factors determining EBF practices in Nepal. The databases PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, MIDIRS, DOAJ, and the NepJOL were searched for peer-reviewed literature published up to December 2021. The JBI quality appraisal checklist was used to assess the quality of studies. Analyses were performed by pooling together studies using the random-effect model, and the I 2 test was used to assess the heterogeneity of the included studies. A total of 340 records were found, out of which 59 full-text were screened. Finally, 28 studies met the inclusion criteria and were selected for analysis. The pooled prevalence of EBF was 43 % (95 % confidence interval: 34–53). The odds ratio for the type of delivery was 1.59 (1.24–2.05), for ethnic minority groups 1.33 (1.02–1.75) and for first-birth order 1.89 (1.33–2.67). We found a lower prevalence of exclusive breastfeeding practice in Nepal compared to the national target. Multifaceted, effective, evidence-based interventions would encourage individuals in the exclusive breastfeeding journey. Incorporating the BEF counselling component into Nepal's existing maternal health counselling package may help promote exclusive breastfeeding practice. Further research to explore the reasons for the suboptimal level of EBF practice would help develop the targeted interventions pragmatically.