Abstract Background Psoroptic mange, caused by Psoroptes ovis mites, is affecting Belgian Blue cattle’s welfare and production potential. The Belgian Blue cattle—known for its high degree of muscling, low feed conversion ratio and high beef quality—is highly susceptible for this disease. Results In this study, we phenotyped 1975 Belgian Blue cattle from more than 100 different groups on commercial beef farms for their psoroptic mange susceptibility. Substantial individual differences were observed within these management groups, with lesion extent differences up to ± 15%. Animal models showed that estimated heritabilities were low for lesion extent and severe lesion extent (0.07 and 0.09, respectively) and 0.12 for the number of mites. A genome wide association study for mange susceptibility revealed signals on BTA6, BTA11, BTA15 and BTA24. In these regions, candidate genes GBA3, RAG2, and TRAF6 were identified. Conclusions Despite the challenges in phenotyping for psoroptic mange due to the timing of screening, the continuous evolution of lesions and different management conditions, we successfully conducted a study on the genetic susceptibility to psoroptic mange in Belgian Blue cattle. Our results clearly indicate that psoroptic mange is under polygenic control and the underlying candidate genes should be studied more thoroughly. This is the first study providing candidate genes for this complex disease. These results are already valuable for Belgian Blue breeding, however, further research is needed to unravel the architecture of this disease and to identify causal mutations.