Field studies were carried out at two sites in 2005 using common lambsquarters seed collected from long-term research plots near Scottsbluff, NE; Fort Collins, CO; and Torrington, WY, to determine the effect of herbicide selection pressure on glyphosate susceptibility. Parental herbicide exposure influenced the level of glyphosate susceptibility exhibited by a subsequent generation. Common lambsquarters selected from historical plots receiving continuous and exclusive use of glyphosate exhibited lower mortality in response to 420 g ae ha−1 glyphosate compared with selections from nonglyphosate treatment histories. Selections from rotating glyphosate treatment histories demonstrated an intermediate tolerance response. Differences in response were also influenced by environmental conditions.