Bread is the main important food product worldwide. In this study, eleven bread formulations were developed by partial substitution of wheat flour with quinoa and tarwi flours, to evaluate the effect on the rheological and pasting properties of mixtures, as well as on the physicochemical and textural properties of the final product. Partial substitution with quinoa flour generated similar thermomechanical and textural properties in the dough, and similar bread technological characteristics related to the control bread (100% wheat). In the case of tarwi, the increase in the concentration of this legume showed a negative effect on the bread quality parameters (specific volume, crumb porosity, textural properties, etc.). A negative technological impact of high percentages of wheat flour substitution by the mixture of both Andean flours was found, but it was contrasted with a positive effect on nutritional quality, particularly evidenced by a high content of proteins and dietary fiber. An optimal formulation considering technological and nutritional quality was obtained, presenting the maximum analyzed substitution level (13.35% quinoa flour and 6.65% tarwi flour). This study showed that these Andean grains are suitable for developing bread of good technological quality and improved nutritional profile, adding value to these underused ancestral flours.