Microwave-assisted heat moisture treatment (MWT) was applied to quinoa grains, a nutritious gluten-free pseudocereal of great interest in food product development, to achieve the physical modification of the quinoa flour. The effect of treating quinoa grains at different initial water contents (WC; 10%, 20%, and 30%) in two operational systems was compared: one open at atmospheric pressure and variable WC (V system), and the other in hermetic containers at constant WC (C system). The morphological structure of the obtained flours and their techno-functional, rheological, and thermal properties were evaluated. MWT proved to be effective in modifying these properties, the main effects probably being caused by protein denaturation and aggregation, and intragranular molecular rearrangements of starch, with disruption of short-range molecular order and even the partial collapse of starch granules in the samples treated at the highest WC. The greatest differences were observed for the 20 and 30% WC treated-samples, particularly when using C system, which increased their water absorption capacity and decreased their foaming, emulsion, and gel-forming capacities. Based on these results, the control of WC and its evolution during MWT of quinoa grains appears to be a viable and effective approach to adapt flour functionality to the needs of food production, allowing a wider range of flour properties depending on the MWT conditions.