Carbon fiber reinforced polymer (CFRP) has excellent mechanical properties and has been widely used in aviation, aerospace, and other fields. Due to the anisotropy of CFRP, it is easy to cause cutter wear during the machining process, resulting in machining defects such as burrs, tearing and delamination. In this paper, a comparative experimental study on the inclined angle milling of CFRP with flat end milling cutter and circular arc milling cutter is carried out. The axial force, cutter wear, the quality of hole entrance and exit and the hole wall micro-morphology of the two cutters under the inclined angle milling method were analyzed. The results show that compared with the tip area of flat end milling cutter, the arc transition area of circular arc milling cutter increases the contact area with the workpiece and reduces the milling axial force. The cutter wear of circular arc milling cutter is mainly concentrated in the arc transition area, and the wear gradually diffuses to the nearby cutting edge. However, the wear of flat end mill cutter is mainly concentrated in the cutter tip area. As the number of holes increases, the cutter tip gradually becomes blunt, and the wear area further expands to the area near the cutter tip. With the increase of cutter wear, the entrance defects of the processing hole of the two cutters are less, the exit of the hole of the circular arc milling cutter has defects such as tearing and burrs. In addition, there are defects such as fiber exposed and cavities on the surface of the hole wall. Compared with the circular arc milling cutter, the flat end milling cutter has more defects at the exit of the hole. At the same time, many surface cavities, pits, and fiber pull-out phenomena on the surface of the hole wall.