The state of Colorado's West Slope Basins are critical headwaters of the Colorado River and play a vital role in supporting Colorado's local economy and natural environment. However, balancing the multi‐sectoral water demands in the West Slope Basins while maintaining crucial downstream deliveries to Lake Powell is an increasing challenge for water managers. Internal variability of the hydroclimatic system and climate change complicate future vulnerability assessments. This work contributes a detailed accounting of multi‐sectoral drought vulnerability in the West Slope Basins and the impacts of drought on downstream deliveries. We first introduce a novel multi‐site Hidden Markov Model (HMM)‐based synthetic streamflow generator to create an ensemble of streamflows for all West Slope basins that better characterizes the region's drought extremes. We capture the effects of climate change by perturbing the HMM to generate an ensemble of streamflows reflecting plausible changes in climate. We then route both ensembles through StateMod, Colorado's water allocation model, to evaluate spatially compounding drought impacts across the West Slope Basins. Our results illustrate how drought events emerging from the system's stationary internal variability in the absence of climate change can significantly impact local water uses and deliveries to Lake Powell, exceeding extreme conditions in the historical record. Further, we find that even modest climate change can cause a regime shift where historically low downstream delivery volumes and extreme drought impacts become routine. These results can inform future Colorado River planning efforts, and our methodology can be expanded to other snow‐dominated regions that face persistent droughts.