Agricultural intensification has been adopted as a viable option for Poverty eradication and hunger, attainment of food security, socio-economic wellbeing as well as sustainable livelihood across the West Africa sub-humid and semi-arid zones. Thus, there is need to identify and address the challenges of sustainable livelihoods in the agriculture-intensive semi-arid and dry sub-humid zones of West Africa. This was addressed through review of relevant literature and analysis of environmental parameters from recent research by the authors to unveil the environmental uncertainties that threaten the sustainability of agriculture and human livelihoods across the ecologically fragile regions of West Africa, using pointers from Nigeria. The research identified the fundamental challenges, adaptation and mitigation approaches to environmental constraints, and requirements for reducing risk, enhance agricultural resilience as well as livelihoods in the zones. This was based on the premise that primarily, the use of adequate and accurately derived environmental information is crucial for increased agricultural productivity, sustainability of economic diversification and human livelihoods and by implication, enhanced regional and national security.