Bread enriched with broccoli stalk powder is proposed as a newly formulated product with potential health benefits. Wheat flour in the bread recipe was enriched with powder obtained from freeze-drying broccoli stalks, a valuable by-product of vegetable processing. The effects of broccoli stalk powder (BSP) supplementation on the physicochemical and sensory properties of bread, as well as its bioactive profile, were evaluated. The results showed an increase in moisture content and acidity with increasing substitution levels from 0% (control bread—BC) to 7%, while some important parameters in terms of consumers’ acceptability decreased (i.e., loaf volume and porosity). Elasticity exhibited moderate variations, with no major influence at lower substitution levels. A small-scale consumer test indicated good scores up to moderate substitution levels (3–5%). The antioxidant activity of broccoli stalk flour (62.13% ± 1.29%) positively influenced the antioxidant activity of bread with 3% BSP, which increased by approximately 4%. The total polyphenol content (TPC) of the bread with 5% BSP, together with its physicochemical and sensory characteristics, suggested that broccoli stalk powder is a promising functional ingredient for bakery applications.