Significance Humans are typically infected with influenza viruses in childhood and then continuously exposed to antigenically distinct influenza virus strains throughout life. Antibody responses elicited by initial influenza virus infections can be boosted upon subsequent exposures with antigenically drifted influenza virus strains. Here, we examined how initial influenza virus infections affect antibody responses against subsequent infections with an unrelated influenza virus subtype. We show that heterosubtypic infections in ferrets and humans boost hemagglutinin stalk antibodies that paradoxically do not bind effectively to the boosting influenza virus strain. We propose that hemagglutinin stalk antibody repertoires are shaped by the specific subtype of influenza virus that an individual encounters early in life, and that this affects susceptibility to heterosubtypic infections later in life.