An efficacious universal influenza vaccine remains a long-sought goal for human health as current vaccines suffer from shortfalls such as mid to low efficacy and the need for yearly revisions in strains use to account for viral drift/shift. Horses undergo bi-annual vaccines for H3N8 equine influenza virus, and surveillance of sera from vaccinees demonstrated very broad reactivity and neutralization to many human seasonal influenza strains. Subsequently, vaccination of mice using the equine H3N8 Kentucky/1/91 strain of equine H3N8 vaccine induced similar broadly reactive and neutralizing serum antibodies to human seasonal strains and to high pathogenicity avian influenza strains. Challenge of mice vaccinated with equine H3N8 or recombinant hemagglutinin (HA) based on the same strain protected vaccinees from high-dose lethal virus challenges. Protection was associated with the presence of neutralizing antibodies to the HA head, esterase, and stem regions that was similar to that of antibodies generated in horses after vaccination. Vaccinated ferrets exhibited similar broadly reactive serum antibody responses that protected vaccinees from clinical signs of infection and viral-induced histopathology after challenge with influenza A/07/2009 (H1N1) pandemic virus. Taken together, these data suggest that vaccination with equine H3N8 vaccine induces broad protection against influenza without the need for non-influenza viral vectors, multiple HAs, or foreign protein scaffolds common to other universal influenza vaccine candidates.