Potential yield losses in grain sorghum due to weed interference based on quantitative data from the major grain sorghum growing areas of the United States of America are reported by the WSSA Weed Loss Committee. Weed scientists and extension specialists who researched weed control in grain sorghum provided data on grain sorghum yield loss due to weed interference in their region. Data were requested from up to 10 individual experiments per calendar year over 10 years between 2007 and 2016. Based on the summarized information, farmers in Arkansas, Kansas, Missouri, Nebraska, South Dakota, and Texas would potentially lose an average of 37, 38, 30, 56, 61, and 60% of their grain sorghum yield with no weed control, and have a corresponding annual monetary loss of US$ 19, 302, 7, 32, 25, and 314 million, respectively. The overall average yield loss due to weed interference was estimated to be 47% for this grain sorghum growing region. Thus, farmers in the USA would lose approximately 5.7 million tonnes of grain sorghum valued at approximately US$ 953 million annually if weeds are not controlled. With each dollar invested in weed management (based on estimated weed control cost of US$ 100 ha-1), there would be a return of US$ 3.80, highlighting the return on investment in weed management and the importance of continued weed science research for sustaining high grain sorghum yield and profitability in the USA.