Identifying factors that drive variation in herbivore effects on plant populations can provide insight for explaining plant distributions and for limiting weeds. Abiotic resource availability to plants is a key explanation for variation in herbivore effects on individual plants, but the role of resources in determining herbivore effects on plant populations is largely unexplored. We tested the hypothesis that soil nutrient availability drives variation in insect and mammal herbivore effects on tall thistle (Cirsium altissimum) population growth. In a Kansas USA restored tallgrass grassland that experienced prescribed fires, we manipulated soil nutrients, through fertilizer addition, and presence of insect and mammal herbivores, using combinations of insecticide and fencing, in experimental plots. Over 7 years, we quantified herbivore damage to reproductive tall thistles, tall thistle seed production and population growth rates. Seed production was reduced by insect herbivores and increased by fertilizer addition, but treatment effects were independent. Herbivore effects on tall thistle population growth depended upon soil nutrients in only one of seven annual transitions. Herbivores reduced thistle population growth in two of three annual transitions that included prescribed fire, whereas they reduced population growth in only one of four transitions without fire. Soil nutrient availability does not provide a general explanation for variation in herbivore effects on tall thistle population growth rates. Disturbance regime may be a more important aspect of ecological context for influencing herbivore effects on tall thistle populations in mesic grasslands.