During the last two decades on a global scale, there has been a significant development of desalination as a strategy to ensure the urban water supply in arid and semi-arid areas. Beyond issues related to the higher economic costs, one of the main barriers that may limit this water source’s development is its supposed negative water quality perception. This research aims to understand better which factors are behind water quality perception in Antofagasta (Chile), where desalinated water was introduced in 2003. Since then, this urban water supply system has increasingly incorporated desalination, creating three parallel areas according to the water sources used in each of them (desalinated water, freshwater and a mix of both). To do so, more than 800 questionnaires to test water quality perception and water consumption habits were conducted in households. Up to six logistic regression models have been implemented to identify which variables better explain water quality satisfaction, risk perception and daily water practices considering the water supply area. It is worth noting that most of this type of research has been carried out in study cases with homogeneous urban water supply systems with conventional water resources. Results indicate that, among other factors, organoleptic water characteristics, such as taste, and socioeconomic status are some of the main factors that explain the perception of water quality and daily practices. In addition, a lower water quality perception and greater risk perception have been identified where desalinated water has been introduced, which makes some households develop averting behaviors to improve water quality, such as boil water.