Background and Purpose: Accurate prediction of functional outcome after stroke would provide evidence for reasonable post-stroke management. This study aimed to develop a machine learning-based prediction model for 6-month unfavorable functional outcome in Chinese acute ischemic stroke (AIS) patient. Methods: We collected AIS patients at National Advanced Stroke Center of Nanjing First Hospital (China) between September 2016 and March 2019. The unfavorable outcome was defined as modified Rankin Scale score (mRS) 3-6 at 6-month. We developed five machine-learning models (logistic regression, support vector machine, random forest classifier, extreme gradient boosting, and fully-connected deep neural network) and assessed the discriminative performance by the area under the receiver-operating characteristic curve. We also compared them to the Houston Intra-arterial Recanalization Therapy (HIAT) score, the Totaled Health Risks in Vascular Events (THRIVE) score, and the NADE nomogram. Results: A total of 1,735 patients were included into this study, and 541 (31.2%) of them had unfavorable outcomes. Incorporating age, National Institutes of Health Stroke Scale score at admission, premorbid mRS, fasting blood glucose, and creatinine, there were similar predictive performance between our machine-learning models, while they are significantly better than HIAT score, THRIVE score, and NADE nomogram. Conclusions: Compared with the HIAT score, the THRIVE score, and the NADE nomogram, the RFC model can improve the prediction of 6-month outcome in Chinese AIS patients.