The aim of the work was to assess the influence of the leavening agent on several technological, chemical, and nutritional characteristics of breads prepared with whole soft wheat (Triticum aestivum L.) flours. As leavening agents in bread-making, baker’s yeast, biga, and sourdough were utilized. Two ancient varieties, Andriolo and Verna, and a modern grain variety, Bologna, were used. Analysis of the obtained breads included the measurement of the phenols content, the antioxidant activity, the in vitro protein and total digestibility, the texture profile, the crumb grain characteristics and the microbial shelf-life test. The results of the principle component analysis of bread features indicated a clustering depending especially on the leavening agent rather than on the employed flour, particularly when sourdough was used. Protein digestibility, crumb grain characteristics, and shelf-life led to the main differences among the samples. Ancient wheat flour displayed similar features when the same leavening agent was applied. Particularly, the use of sourdough levelled the differences due to flour, leading to breads with similar technological and nutritional characteristics. The findings highlighted a marked effect of the leavening agent on bread final characteristics.