Functional diffusion mapping (fDM) has shown promise as a sensitive imaging biomarker for predicting survival in initial studies consisting of a small number of patients, mixed tumor grades, and before routine use of anti-angiogenic therapy. The current study tested whether fDM performed before and after radiochemotherapy could predict progression-free and overall survival in 143 patients with newly diagnosed glioblastoma from 2007 through 2010, many treated with anti-angiogenic therapy after recurrence. Diffusion and conventional MRI scans were obtained before and 4 weeks after completion of radiotherapy and concurrent temozolomide treatment. FDM was created by coregistering pre- and posttreatment apparent diffusion coefficient (ADC) maps and then performing voxel-wise subtraction. FDMs were categorized according to the degree of change in ADC in pre- and posttreatment fluid-attenuated inversion recovery (FLAIR) and contrast-enhancing regions. The volume fraction of fDM-classified increasing ADC(+), decreasing ADC(-), and change in ADC(+/-) were tested to determine whether they were predictive of survival. Both Bonferroni-corrected univariate log-rank analysis and Cox proportional hazards modeling demonstrated that patients with decreasing ADC in a large volume fraction of pretreatment FLAIR or contrast-enhancing regions were statistically more likely to progress earlier and expire sooner than in patients with a lower volume fraction. The current study supports the hypothesis that fDM is a sensitive imaging biomarker for predicting survival in glioblastoma.