The early 2-factor (E2F) family of transcription factors, including E2F1 through 8, plays a critical role in apoptosis, metabolism, proliferation, and angiogenesis within glioblastoma (GBM). However, the specific functions of E2F transcription factors (E2Fs) and their impact on the malignancy of Bevacizumab (BVZ)-responsive GBM subtypes remain unclear. This study used data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI), and Gene Expression Omnibus (GEO) to explore the impact of eight E2F family members on the clinical characteristics of BVZ-responsive GBM subtypes and possible mechanisms of recurrence after BVZ treatment. Using machine learning algorithms, including TreeBagger and deep neural networks, we systematically predicted and validated GBM patient survival terms based on the expression profiles of E2Fs across BVZ-responsive GBM subtypes. Our bioinformatics analyses suggested that a significant increase in E2F8 post-BVZ treatment may enhance the function of angiogenesis and stem cell proliferation, implicating this factor as a candidate mechanism of GBM recurrence after treatment. In addition, BVZ treatment in unresponsive GBM patients may potentially worsen disease progression. These insights underscore that E2F family members play important roles in GBM malignancy and BVZ treatment response, highlighting their potential as prognostic biomarkers, therapeutic targets, and recommending precision BVZ treatment to individual GBM patients.