In March 2024, clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses were first detected in U.S. dairy cattle. Similar viruses have since caused 66 zoonotic human infections. To assess changes to zoonotic potential, we characterized A(H5N1) clade 2.3.4.4b viruses isolated from cows’ milk and birds. Bovine-derived viruses were lethal in mice and ferrets and transmitted to direct but not airborne contact ferrets. All viruses replicated in human bronchial epithelial cells despite preferentially binding avian virus-like receptors. The bovine-derived viruses remained susceptible to FDA-approved antivirals and were neutralized by sera from ferrets vaccinated with WHO CVVs or humans vaccinated with clade 2.3.4.4c vaccine. While 2.3.4.4b viruses induce severe disease in mammalian models, they retain many avian virus-like characteristics. Combined, we conclude that the risk of contemporary bovine-derived viruses to humans not in contact with affected animals is low. However, heightened vigilance remains essential to promptly detect and respond to any changes.