The purpose of this study was to explore the diagnostic value of different sequence scanning of nonparametric variable model-based cranial magnetic resonance imaging (MRI) for ischemic stroke. A histogram analysis-based nonparametric variable model was proposed first, which was compared with the parametric deformation (PD) model and geometric deformation (GD) model. Then, 116 patients with acute ischemic stroke were selected as the research subjects. Routine MRI (T2WI, T1WI, FLAIR, DWI, SWI, and 3D TOF MRA) and MR SCALE-PWI were performed. The results showed that the nonparametric variable model algorithm was relatively complete in the actual segmentation results of MRI images, and the display clarity of lesions was better than PD and GD algorithms. The diagnostic sensitivity, specificity, and overall performance of the variable model algorithm were significantly higher than those of the other two algorithms ( P < 0.05 ). According to ROC curve analysis, the AUC areas of DWI, SWI, 3D TOF MRA, and MR SCALE-PWI for the diagnosis of ischemic penumbra were 0.793, 0.825, 0.871, and 0.933, respectively. In summary, the segmentation results of MRI images by the nonparametric variable model based on histogram analysis were relatively complete, and the clarity of lesions was better than that of the traditional model. MRI images can effectively identify the occurrence of ischemic stroke. Moreover, MR SCALE-PWI had a good early identification effect on ischemic penumbra, which can reduce unnecessary treatment for patients.