Utilizing CRISPR/Cas9 STAT3 knockout (STAT3‐KO) in GBM cells and STAT3‐KO cells restored with wild‐type (WT) STAT3 or with phosphorylation‐defective STAT3 mutants, we demonstrate that STAT3 activation suppresses autophagy, which may be exploitable therapeutically. Here, STAT3 is linked to glioblastoma.