The use of barley flour in bread making is limited because barley flour decreases the sensory characteristics of bread. This study aimed to increase the nutraceutical potential of barley bread without affecting consumer acceptance. Crumb structure, and physical and sensory characteristics were analyzed in breads in which wheat flour was replaced by barley flour (0%, 40%, 50%, 60% and 100%). The bread in which 60% wheat flour was substituted by barley flour was selected and analyzed for its proximate composition, dietary fiber, total phenolic content and antioxidant capacity. This formulation increased the contents of insoluble fiber, soluble fiber, total phenolic compounds and antioxidant capacity of wheat bread by 700%, 200%, 41.5% and 45%, respectively. However, judges objected to the taste of the selected barley bread, thus the addition of Parmesan cheese, oregano or sesame seeds was tested to improve the sensory qualities of bread. The addition of sesame seeds (4 g/100 g, flour basis) enhanced the sensory characteristics of bread besides to increasing its total phenolic content and antioxidant activity by 100% and 130%, respectively, compared to those of the wheat bread. Therefore, the addition of sesame seeds increased the consumer acceptance of the high-barley bread and the potential health benefits of this product.