The Southern Altiplano of Bolivia is the world-leader in quinoa export. In these arid highlands, quinoa yield is largely influenced by on-going changes affecting both climate drivers and land-use practices. We developed a simple “what-if” simulation model for anticipating such changes in quinoa yields over three time-slices: a recent past (1961-2000), a near future (2046-2065), and finally a remote one (2081-2100). Outputs from a global climate model (GCM) were used as drivers for projections of regional climate patterns and for providing risk information. For tackling further problems arising from our limited understanding of what the local-level impacts of climate change are likely to be in this arid mountain area, we decided to consider a grid level area centered on the salar of Uyuni, a region experiencing marked changes in climate and land-use for the past four decades. Local land-use change scenarios were derived from aerial photographs and data from high-resolution remote-sensing validated by ground truth observations on sample areas representative of the region. Climate change scenarios were linked to our yield model composed of a soil water balance model coupled with a simple crop growth component. The daily climate from GCM runs has been used for driving the soil water balance model and calculating the drought severity that the crop might undergo. At the field plot level, the yield index (defined as the the simulated yield relative to a fixed yield potential) depends on soil drought, mean air temperature that largely affects carbon assimilation through photosynthesis, and minimal temperature that impairs the yield during frost nights. At the landscape scale, a mosaic of three land units is considered: cerros (steep slopes), faldas (gentle slopes in piedmonts) and pampas (flat plains). We simulated 2-year crop cycles taking into account complementarities among these landscape units. In each land unit, growth efficiency parameters are affected by the decline in the biological potential of the land. These parameters parallel the rate of encroachment of the quinoa crop, the subsequent decline of pasture lands in the pampa area and the soil aeolian erosion caused by such intensification. Results show an on-going decrease in the occurrence of frost that will be followed by an increasing drought frequency in the forthcoming decades. Long-term increase in soil dryness associated with a decline in the biological potential of the land may largely impair the sustainability of this area. This type of analysis, although speculative, provides insights which can assist research and development organizations target options for sustainability in crop production.