The use of biological control insects is a promising option for suppressing spotted knapweed, a nonindigenous perennial forb that infests more than 3 million hectares of North American rangeland. Efficacy increases when spotted knapweed is attacked by more than one phytophagous insect; however, combined herbivory by biological control insects has not achieved widespread suppression of spotted knapweed in North America. Here we expand the concept of combined herbivory beyond two or more species of biological control insects to include a vertebrate herbivore, specifically targeted grazing by domestic sheep. Our experiment on foothill rangeland in northwestern Montana evaluated spotted knapweed response to three treatments: (1) biological control insects only, (2) biological control insects + targeted sheep grazing applied in late July (spotted knapweed in late bud–early flower stage), and (3) biological control insects + targeted sheep grazing applied in mid-August (spotted knapweed in full-flower stage). We combined targeted sheep grazing with herbivory by three species of biological control insects: knapweed flower weevil, knapweed root weevil, and sulfur knapweed root moth. Treatments were applied during four consecutive years (2009 to 2012). Spotted knapweed fitness was suppressed more where targeted sheep grazing and biological control insects were combined vs. areas treated with biological control insects alone. Combined herbivory was effective when targeted sheep grazing was applied during either late July or mid-August, but July grazing was more effective. Spotted knapweed produced 96 to 99% fewer viable seeds in sheep-grazed areas. After 4 yr of treatment, total spotted knapweed plant density (seedlings, juvenile, and adult plants) was 86% less in July-grazed areas and 61% less in August-grazed areas than in areas treated with biological control insects alone. Combined herbivory by targeted sheep grazing and biological control insects reduced adult plant density and prevented compensatory recruitment of spotted knapweed, but treatment with biological control insects alone did not.