Long-term data sets are rare in agriculture, and the impact of plant diseases on food production is challenging to measure, which makes it difficult to assess the impact of policy changes or research-based disease control efforts. Despite this challenge, it is clear that one of the largest impacts of biological research on food security over the past century has been in production of vegetatively propagated fruit and vegetable crops such as potato. The yield and quality of these crops is higher in countries that have effective plant propagation and certification systems. Of these systems, seed potato production and certification is among the most developed. We analyzed a dataset from a century-old seed potato certification program in Wisconsin to assess the efficacy for potato disease control and the cost of this program compared to other disease control and potato production costs. We found that over the past century, certification has gradually reduced the incidence of mechanically transmitted vascular potato pathogens that lack insect vectors to undetectable levels, and much of this reduction occurred prior to the use of tissue culture and the development of immunoassays. Rejection of seed lots from certification is now rare, with Potato virus Y (PVY), a virus spread nonpersistently by numerous, noncolonizing aphid species, and farmer errors being the main causes of rejection. PVY level increases occurred in 2000, coincident with the first detection of a new invasive vector, soybean aphid, in the Midwest. The increased PVY incidence was more pronounced in varieties that exhibit mild foliar symptoms. Starting in 2004, a decrease in PVY incidence occurred following comprehensive science-based changes to early generation seed potato production. The cost of the certification program has not increased in two decades, and the fees charged are comparable to those in 1913. The cooperative nature of the seed potato certification program has contributed to its sustainability across generations. However, looming soilborne disease problems are not easily addressed by certification and will likely cause significant challenges in the future.