Potato is the third most important staple food crop globally following rice and wheat. In the United States, potato is grown on approximately 410,000 ha with a farm-gate value of US$1,032 million. In Canada, potato is grown on approximately 134,000 ha with a farm-gate value of US$235 million. The objective of this manuscript, compiled by the Weed Science Society of America Weed Loss Committee, was to estimate potato yield loss caused by weed interference. Potato yield data from weedy and weed-free plots (or plots with >95% weed control) was obtained from researchers working on weed management in potato in the United States and Canada or from published manuscripts from 2000 to 2018. Potato yield loss from weed interference was 12% to 61% when no weed management tactics were implemented. The average yield loss for all states/provinces (where data was obtained) due to weed interference was 44%. Weed interference would cause a farm-gate loss of approximately US$465 million and US$61 in the United States and Canada, respectively, if weeds are not controlled. These results indicate that weed management is critical for successful potato production, and that an ongoing need for research exists on weed management in this crop.