Objectives: This pilot study compared the diagnostic performances of DSC-MRI and FAPI PET in differentiating tumor progression (TP) and treatment-related change (TRC) in isocitrate dehydrogenase (IDH) wild-type glioblastoma during follow-up. Methods: IDH wild-type glioblastoma patients who underwent DSC-MRI and FAPI PET were analyzed retrospectively. TP and TRC lesions were confirmed through radiological and clinical follow-up, with a median follow-up period of 8 months (2–12 months). The differences in DSC-MRI (CBVmax, CBVmean, and rCBVmean) and FAPI PET (SUVmax, SUVmean, and TBR SUVmean) parameters between TP and TRC were compared. ROC curve analyses were performed to assess the diagnostic performance. DeLong's test evaluated the differences in AUCs. Results: Twelve patients (6 men and 6 women, aged 33–70) with IDH wild-type glioblastoma were enrolled. Totally 18 lesions (8 TRC and 10 TP) were detected. All DSC-MRI and FAPI PET parameters were significantly higher in the TP than in the TRC. CBVmean showed the highest diagnostic performance among all parameters. However, the DeLong test revealed no significant difference in diagnostic performance between DSC-MRI and FAPI PET parameters. Conclusions: Although the CBVmean has excellent diagnostic performance in differentiating TP from TRC, FAPI PET parameters were statistically found to have similar diagnostic performance. FAPI PET may be an alternative modality for patients with IDH wild-type glioblastoma who are unable to undergo DSC-MRI. However, further prospective large cohort studies and clinical validation are necessary.