Livestock guard dogs (LGDs; Canis familiaris) have been widely adopted by domestic sheep (Ovis aries) producers because they reduce predation by wild carnivores. LGDs were originally used in the United States to reduce coyote (Canis latrans) depredations, but their efficacy against a suite of large carnivores, including wolves (Canis lupus), brown bears (Ursus arctos), black bears (Ursus americanus), and cougars (Puma concolor), and whether specific breeds perform better than others remains unclear. To assess breed-specific effectiveness at reducing depredations from a suite of livestock predators, we compared survival rates of sheep protected by different breeds of LGDs, including three breeds from Europe (Turkish kangal, Bulgarian karakachan, and Portuguese cão de gado transmontano) and mixed-breed LGDs, “whitedog,” common in the United States. With the help of participating sheep producers, we collected cause-specific mortality data from domestic sheep in Idaho, Montana, Oregon, and Wyoming between 2013 and 2016. All three of the novel breeds of LGD tested were associated with overall reductions in sheep depredation relative to whitedogs, ranging from 61% to 95% (P < 0.05). In terms of predator-specific effectiveness, the Turkish kangal was associated with decreases in depredation from cougars (e^β = 0.31, 95% CI = 0.10–0.94, P = 0.04), black bears (e^β = 0.33, 95% CI = 0.28–0.37, P < 0.01), and coyotes (e^β = 0.56, 95% CI = 0.35–0.90, P = 0.02). The Bulgarian karakachan was associated with a decrease in coyote depredations (e^β = 0.07, 95% CI = 0.01–0.49, P < 0.01). The Portuguese transmontano was not associated with significant reductions in depredation hazard for any specific predator. Although variations in breed-specific effectiveness were subtle and nuanced, these findings will help livestock producers and wildlife managers make tailored decisions about how best to incorporate different breeds of LGD into sheep grazing regimes.