The study examined the expansion of sugarcane monoculture over the period 1957-2010 and its implications for land degradation and land management measures in the semi-arid northern Main Ethiopian Rift Valley. It used multi-scale and multi-temporal imageries aided by qualitative surveying to investigate the dynamics of land use and cover changes. The study applied both a pixel-based supervised classification and feature extraction methods at subclass levels and merged them into major compatible and comparable land use and cover groups. The results indicated a substantial transformation in the landscape over 53years (1957-2010), which is attributed to expansion of sugarcane plantation, saline lake water, and smallholder farmland and settlements. The land use and cover changes culminated in reduction of native vegetation cover and biodiversity loss, encroachment of non-native species, and occurrence of soil salinity. Major causes that justify the changes include (1) macro-economic changes and policy shifts towards agricultural development, (2) change in underground hydrology, (3) population growth, and (4) sedentarization of the traditional pastoral community. Proper measures should aim at addressing the trade-off between economic development and environmental sustainability. Moreover, management opportunities should base on the understanding of socioeconomic and biophysical settings and balance the sustenance of the local people and ecological function of the area.