The Gamo Highlands in Ethiopia are characterized by complex topography and lakes. These modulate the mesoscale and synoptic scale weather systems. In this study, we analyzed the temporal and spatial variations in weather as function of topography and season and their impact on potato crop growth. To determine how crop growth varies with elevation, we installed a network of six automatic weather stations along two transects. It covers a 30-km radius and 1800-m elevation difference. We conducted a potato field experiment near the weather stations. We used the weather observations as input for a crop model, GECROS. Data analysis showed large differences between weather in February and May. February is more dominated by mesoscale circulations. The averaged February diurnal patter shows a strong east to southeast lake breezes and, at night, weak localized flows driven by mountain density flows. In contrast, in May, the synoptic flow dominates, interacting with the mesoscale flows. The GECROS model satisfactorily predicted the elevational gradient in crop yield. Model sensitivity experiments showed that belg-averaged precipitation distribution gave the highest yield, followed by exchanging May weather observations with April.