Variation in crop–weed interference relationships has been shown for a number of crop–weed mixtures and may have an important influence on weed management decision-making. Field experiments were conducted at seven locations over 2 yr to evaluate variation in common lambsquarters interference in field corn and whether a single set of model parameters could be used to estimate corn grain yield loss throughout the northcentral United States. Two coefficients (I and A) of a rectangular hyperbola were estimated for each data set using nonlinear regression analysis. The I coefficient represents corn yield loss as weed density approaches zero, and A represents maximum percent yield loss. Estimates of both coefficients varied between years at Wisconsin, and I varied between years at Michigan. When locations with similar sample variances were combined, estimates of both I and A varied. Common lambsquarters interference caused the greatest corn yield reduction in Michigan (100%) and had the least effect in Minnesota, Nebraska, and Indiana (0% yield loss). Variation in I and A parameters resulted in variation in estimates of a single-year economic threshold (0.32 to 4.17 plants m−1 of row). Results of this study fail to support the use of a common yield loss–weed density function for all locations.