Desalination is increasingly popular for ensuring potable water. Using the City Blueprint Approach methodology in Antofagasta, Chile, we identify the barriers, opportunities and transferable lessons that can enhance governance capacity towards the successful implementation of desalination. Antofagasta’s desalinization programme is associated with negative water-quality perceptions, environmental impacts and high energy demands. Additionally, the supply has a moderate impeding influence on water-use efficiency efforts. Consequently, we draft a priority ladder for water provision in water-scarce regions to: ensure access; reduce consumption; apply reuse; and explore renewable water resources – and if a combination of previous steps is insufficient, desalination may be applied to meet water supply shortages.