Bread is one of the most consumed products around the world, justifying the continuous research and development activities on how to improve its sensory, chemical and industrial characteristics. Volatile organic compounds (VOCs) play a key role in this regard because they take shape during the leavening process and are enhanced upon baking. In this study, proton-transfer reaction mass spectrometry (PTR-MS), coupled to a time-of-flight (ToF) mass analyser, was undertaken in order to analyse the effects of Saccharomyces cerevisiae strains as well as the type of wheat flour used in the bread-making process on VOC production. The results showed a greater impact of yeast strains over the expected flour influence. This observation was confirmed when the leavened dough samples were baked and the volatile profiles determined. However, the peak-by-peak monitoring, followed by a tailored statistical approach, revealed not only the effect of changing ingredients but also different kinds of yeast/flour interaction. Such findings shed a new light on the selection of ingredients for each bread recipe depending on the desired volatile profile of the baked product and on the potential of PTR-MS in analysing protechnological microbes/matrix interaction during food fermentations.