Farmland abandonment is a common phenomenon worldwide, including in the Gandaki River Basin (GRB) in the central Himalayas. This study examined the status of farmland abandonment, along with its trends and determinants, based primarily on interviews with 639 households in different physiographic regions: Mountain, Hill, Tarai and Gangetic Plain (GP). Binary logistic regression was used to examine the contributions of various factors of farmland abandonment. The results indicate that nearly 48%, 15%, 4%, and 16% of total farmland (khet and bari) in the Mountain, Hill, Tarai and GP regions, respectively, has been abandoned. Such differences in the proportion of farmland abandonment among the regions are mainly due to variations in biophysical conditions, agricultural productivity, access to infrastructure facilities, off-farm employment opportunities, and the occurrence of natural hazards. The major determinants for farmland abandonment were also found to vary within the region. Distance from market centers to residence, reduction in the labor force as a result of migration, and household head age were found to be significant factors in farmland abandonment in the Mountain region. Similarly, in the Hill region, eight significant factors were identified: distance from market centers to residence, distance from residence to farmland, lack of irrigation facilities (p = 0.004), reduction in labor force (p = 0.000), household head occupation, lack of training for household head and size of bari land. Household head occupation and household head age were found to play significant roles for farmland abandonment in the Tarai region. In the GP region, distance to market centers and lack of irrigation facilities had positive relationships with farmland abandonment. It is suggested that specific policies addressing the differences in physiographic region, such as horticulture and agroforestry for the Mountain and Hill regions and crop diversification and the adaptation of drought tolerant species with improvement in irrigation systems for the GP region, need to be formulated and implemented in order to utilize the abandoned farmland and have environmental, economic, and sustainable benefits.