Malignant cerebral edema (MCE) after an ischemic stroke results in a poor outcome or death. Early prediction of MCE helps to identify subjects that could benefit from a surgical decompressive craniectomy. Net water uptake (NWU) in an ischemic lesion is a predictor of MCE; however, CT perfusion and lesion segmentation are required. This paper proposes a new Image Patch-based Net Water Uptake (IP-NWU) procedure that only uses non-enhanced admission CT and does not need lesion segmentation. IP-NWU is calculated by comparing the density of ischemic and contralateral normal patches selected from the middle cerebral artery (MCA) area using standard reference images. We also compared IP-NWU with the Segmented Region-based NWU (SR-NWU) procedure in which segmented ischemic regions from follow-up CT images are overlaid onto admission images. Furthermore, IP-NWU and its combination with imaging features are used to construct predictive models of MCE with a radiomics approach. In total, 116 patients with an MCA infarction (39 with MCE and 77 without MCE) were included in the study. IP-NWU was significantly higher for patients with MCE than those without MCE (p < 0.05). IP-NWU can predict MCE with an AUC of 0.86. There was no significant difference between IP-NWU and SR-NWU, nor between their predictive efficacy for MCE. The inter-reader and interoperation agreement of IP-NWU was exceptional according to the Intraclass Correlation Coefficient (ICC) analysis (inter-reader: ICC = 0.92; interoperation: ICC = 0.95). By combining IP-NWU with imaging features through a random forest classifier, the radiomics model achieved the highest AUC (0.96). In summary, IP-NWU and radiomics models that combine IP-NWU with imaging features can precisely predict MCE using only admission non-enhanced CT images scanned within 24 h from onset.