Common lambsquarters is an important annual weed of many crops world-wide. Ascochyta caulina is a plant pathogenic fungus that, under natural conditions, causes necrotic spots on the leaves and stems of Chenopodium species. The objective of this study was to evaluate the effect of weed growth stage, relative humidity, dew period, and temperature on the infection of A. caulina isolates against common lambsquarters. In greenhouse experiments, replicated groups of common lambsquarters plants were sprayed with different isolates of A. caulina 2, 3, 4, 5, and 6 wk after emergence. Both disease severity and pathogen-induced dry weight reduction decreased with plant age. The efficacy of all isolates tested was reduced by high leaf-to-air vapor-pressure deficit. Disease severity was more responsive to relative humidity than temperature. However, a minimum dew period of 6 h was required to cause significant disease severity in common lambsquarters. Among all tested A. caulina isolates, W90–1 gave the highest disease scores under all conditions, with the exception of temperatures ≤15 C.