Food and nutrition insecurity continues to be the main challenges in Sub-Saharan Africa (SSA). The traditional tillage practice with a rainfed system, and poor soil and water management resulted in soil degradation and low productivity. In this study; field experiment, biophysical model, and spatial analysis were used to identify and evaluate a potential solution for small-scale agriculture in the region; particularly in Ethiopia, Ghana, and Tanzania. Multi-Criteria Evaluation (MCE) technique was used to assess irrigable land and feasibility of water-lifting technologies for the Lake Tana Basin of Ethiopia, followed by determining irrigation potential. Biophysical data were collected from the field experiment in SSA to evaluate the impacts of conservation agriculture (CA) with drip irrigation on vegetable yield and irrigation water use. The Agricultural Policy / Environmental eXtender (APEX) model was verified using field-scale data and used to evaluate the impacts of CA with drip irrigation on water management and crops. The APEX model and MCE technique were to upscale field-scale crop production to the national level, followed by determining irrigation potential of groundwater. About 345,000 ha and 135,000 ha of lands in Lake Tana Basin were found irrigable from surface and groundwater sources; low-flow of rivers and groundwater can satisfy up to about 1.2% and 3.5% of the irrigable lands, respectively. The Rope pump has the highest applicability in Lake Tana Basin (26%) for the use of groundwater. From the field experiment, a significant vegetable yield increase was observed in Ethiopia (9-184%) and Ghana (18-99%) under CA; except in Tanzania possibly due to waterlogging. On the other hand, CA significantly reduced irrigation water use (18-47%) for various vegetables. The model result depicted the improvement of water management; the reduction of evapotranspiration (up 49%) and runoff (up to 62%), and the increase in soil moisture and percolation. The average fresh vegetable yield ranges from 1.8--2.8 t/ha; 1.4--2.2 t/ha; 5.5--15.7 t/ha. and 8.3--12.9 t/ha for garlic, onion, tomato, and cabbage, respectively. Groundwater can support about 1.4 - 3.5 Mha of land to produce vegetables. CA with drip irrigation has the potential to intensify food production in SSA.