Potato virus Y (PVY) is an economically important and reemerging potato pathogen in North America. PVY infection reduces yield, and some necrotic and recombinant strains render tubers unmarketable. Although PVY^O is the most prevalent strain in the United States, the necrotic and recombinant strains PVY^NTN and PVY^N:O are becoming more widespread. Infection rates in aphidinoculated (Myzus persicae (Sulzer)) and mechanically inoculated plants were compared across two potato genotypes (’Yukon Gold’ and A98345-1), three PVY strains (PVY^O, PVY^N:O, and PVY^NTN), and two growth stages at inoculation (pre- and postflowering). Susceptibility of genotypes was measured as infection rate using a double-antibody sandwich-enzyme-linked immunosorbent assay; virus titer and tuber mass also were recorded from the infected plants. Yukon Gold generally was more susceptible than A98345-1 to all three PVY strains, especially following mechanical inoculation. Within genotypes, Yukon Gold was most susceptible to PVY^O and A98345-1 was most susceptible to PVY^N:O. Plants exhibited age-based resistance, with both genotypes showing higher susceptibility at the prethan postflowering stage. The overall ranking pattern of virus titer in infected plants was PVY^O > PVY^NTN > pvy^N:O; across all three strains, infected Yukon Gold had higher titer than infected A98345-1 plants. Yukon Gold plants had lower tuber mass than A98345-1 when infected, and there were differences between the two inoculation methods in regard to tuber mass for the three stains. The results showed differences in infection response between inoculation methods and as a function of genotype, strain, inoculation stage, and their interactions. These factors should be considered when screening genotypes for resistance.