Tuning the parameters of Computerized Numerical Control (CNC) is essential for practical manufacturers. Well configured parameters ensure the efficiency of production and the accuracy of the products. However, with the abrasive wear on the flank of the milling cutter, the milling processing parameters should re-configure to adapt to the increment of the abrasive wear. This paper aims to propose a method to predict the abrasive wear rate increment on the flank of the milling cutter and optimize the processing parameters of CNC milling. Firstly, we set a cutting data acquisition system to sample the processing time and cutting force among X, Y coordinates based on the five-factor and four-level orthogonal experiments. Then, the sampled cutting force data increment is transformed into the abrasive wear rate increment by applying the incremental model. Next, five processing parameters for CNC milling are optimized by the gray relational method, which takes the limited abrasive wear rate increment of the flank face and the non-increasing processing time as the constrained conditions. We obtain the relationship between five processing parameters and abrasive wear rate increment. We also find the basic principle of selecting process parameters is to reduce the abrasive wear rate without increasing the processing time. The experimental results verify that the optimized process parameters make the gray relational degree increase by 0.02, and the abrasive wear rate increment decreases by 0.42432 × 10−10 mm3/s without affecting the production efficiency. In the prediction section, by applying the Back Propagation (BP) neural network, we obtain an accurate prediction model from measurable five factors to the abrasive wear increment on the flank of the milling cutter. The maximum error between the predicted value and the actual value is 0.0003, and the predicted value curve fits well with the actual value curve. From the perspective of abrasive wear rate increment prediction, it provides a new idea for online tool wear monitoring.