(1) Background: The objective of this study was to determine whether arterial spin labeling (ASL), amide proton transfer (APT), or their combination could distinguish between patients with a low and high modified Rankin Scale (mRS) and forecast the effectiveness of the therapy; (2) Methods: Fifty-eight patients with subacute phase ischemic stroke were included in this study. Based on cerebral blood flow (CBF) and asymmetry magnetic transfer ratio (MTRasym) images, histogram analysis was performed on the ischemic area to acquire imaging biomarkers, and the contralateral area was used as a control. Imaging biomarkers were compared between the low (mRS 0–2) and high (mRS 3–6) mRS score groups using the Mann–Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the potential biomarkers in differentiating between the two groups; (3) Results: The rAPT 50th had an area under the ROC curve (AUC) of 0.728, with a sensitivity of 91.67% and a specificity of 61.76% for differentiating between patients with low and high mRS scores. Moreover, the AUC, sensitivity, and specificity of the rASL max were 0.926, 100%, and 82.4%, respectively. Combining the parameters with logistic regression could further improve the performance in predicting prognosis, leading to an AUC of 0.968, a sensitivity of 100%, and a specificity of 91.2%; (4) Conclusions: The combination of APT and ASL may be a potential imaging biomarker to reflect the effectiveness of thrombolytic therapy for stroke patients, assisting in guiding treatment approaches and identifying high-risk patients such as those with severe disability, paralysis, and cognitive impairment.