Avian H5N1 influenza viruses are circulating widely in cattle and other mammals and pose a risk for a human pandemic. Previous studies suggest that older humans are more resistant to H5N1 infections due to childhood imprinting with other group 1 viruses (H1N1 and H2N2); however, the immunological basis for this is incompletely understood. Here we measured H5N1 antibody responses in sera from 157 individuals born between 1927 and 2016. We show that antibody titers to historical and recent H5N1 strains are highest in older individuals and correlate more strongly with birth year than with age, consistent with immune imprinting. Young children, who were likely not yet exposed to seasonal influenza viruses, had low levels of H5-specific antibodies. We also measured H5N1 antibody responses in sera from 100 individuals before and after receiving an A/Vietnam/1203/2004 H5N1 vaccine. We found that both younger and older humans produced H5-reactive antibodies to the A/Vietnam/1203/2004 vaccine strain and to a contemporary clade 2.3.4.4b strain, with higher seroconversion rates in young children who had lower levels of antibodies before vaccination. These studies suggest that younger individuals might benefit more from vaccination than older individuals in the event of an H5N1 pandemic.