The failure progression of coated carbide tools in end milling of Inconel 718 superalloy was investigated. Tool wear was measured and failure mechanisms were discussed in the experimental process periodically. The experimental results indicated that the tool failure mechanisms were synergistic interaction among abrasive wear, adhesive wear, and fatigue wear. However, abrasive wear and adhesive wear were the main failure mechanisms at the beginning, fatigue wear prevailed the upper hand around the time when edge chipping appeared, and after edge chipping abrasive wear and adhesive wear dominated until the failure time. In addition, the macroscopic failure of the cutting tools is closely correlated to the nucleation and propagation of the crack under cyclic mechanical and thermal impact forces. Mechanical fatigue wear was the key form of fatigue wear at lower cutting speed, while at higher cutting speed thermal fatigue wear was the dominant fatigue wear.