Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b virus was identified in 4 cull dairy cows condemned by the U.S. Department of Agriculture because of pneumonia with accompanying systemic changes. Histologic findings were bronchopneumonia in 3 cows and embolic pneumonia and nephritis in 1 cow. In addition to detection of HPAI A(H5N1) virus by reverse-transcription real-time PCR in various formalin-fixed, paraffin-embedded tissues, influenza A virus was detected by immunohistochemistry and in situ hybridization in the pulmonary respiratory epithelium of 2 of the cows with bronchopneumonia and in renal medullary tubules of the cow with nephritis. A PCR panel screening for common bovine respiratory pathogens in the cows with bronchopneumonia revealed variable coinfections with Histophilus somni, Pasteurella multocida, Mannheimia haemolytica, Mycoplasmopsis bovis, and bovine coronavirus. We describe the distribution of HPAI A(H5N1) virus in naturally infected cows while highlighting the need for research on the roles of coinfection and immune response in influenza viral replication.