Multivariate linear mixed models (mvLMMs) are widely applied for genome-wide association studies (GWAS) to detect genetic variants affecting multiple traits with correlations and/or different plant growth stages. Subsets of multiple sorghum populations, including the Sorghum Association Panel (SAP), the Sorghum Mini Core Collection and the Senegalese sorghum population, have been screened against various sorghum diseases such as anthracnose, downy mildew, grain mold and head smut. Still, these studies were generally performed in a univariate framework. In this study, we performed GWAS based on the principal components of defense-related multi-traits against the fungal diseases, identifying new potential SNPs (S04_51771351, S02_66200847, S09_47938177, S08_7370058, S03_72625166, S07_17951013, S04_66666642 and S08_51886715) associated with sorghum’s defense against these diseases.