Computational fluid dynamics (CFD) is widely employed to predict hemodynamic characteristics in arterial models, while not friendly to clinical applications due to the complexity of numerical simulations. Alternatively, this work proposed a framework to estimate hemodynamics in vessels based on angiography images using machine learning (ML) algorithms. First, the iodine contrast perfusion in blood was mimicked by a flow of dye diffusing into water in the experimentally validated CFD modeling. The generated projective images from simulations imitated the counterpart of light passing through the flow field as an analogy of X-ray imaging. Thus, the CFD simulation provides both the ground truth velocity field and projective images of dye flow patterns. The rough velocity field was estimated using the optical flow method (OFM) based on 53 projective images. ML training with least absolute shrinkage, selection operator and convolutional neural network was conducted with CFD velocity data as the ground truth and OFM velocity estimation as the input. The performance of each model was evaluated based on mean absolute error and mean squared error, where all models achieved or surpassed the criteria of 3 × 10−3 and 5 × 10−7 m/s, respectively, with a standard deviation less than 1 × 10−6 m/s. Finally, the interpretable regression and ML models were validated with over 613 image sets. The validation results showed that the employed ML model significantly reduced the error rate from 53.5% to 2.5% on average for the v-velocity estimation in comparison with CFD. The ML framework provided an alternative pathway to support clinical diagnosis by predicting hemodynamic information with high efficiency and accuracy.