<p>GH4169 is a high-performance nickel-based superalloy that exhibits exceptional mechanical properties and thermal stability, making it widely applicable in the aerospace industry and other domains. However, due to its unique material microstructure and low cutting performance, conventional milling is often faced with problems such as serious work hardening, and serious tool wear. Based on these challenges, this paper proposes the application of longitudinal-torsional ultrasonic vibration-assisted side milling (LTUVSM) for the machining of GH4169 superalloy. The study primarily focused on the ultrasonic vibration’s influence on tool wear behavior during GH4169 side milling, encompassing milling force, tool’s life, wear morphology of tool, and the potential wear mechanisms of tool in both LTUVSM and conventional side milling (CSM). The results indicate that as milling time increases, the <i>F</i>_<i>x</i> values for both CSM and LTUVSM exhibit an increasing trend. However, compared with CSM, the growth rate of <i>F</i>_<i>x</i> in LTUVSM is slower. Additionally, LTUVSM demonstrates a relatively lower tool wear rate. Within the same processing duration, LTUVSM achieves a 20% improvement in processing efficiency compared to CSM while also exhibiting a longer tool life. Under CSM conditions, the predominant tool wear morphologies include chipping, adhesion, coating delamination, scratching, crater wear, and built-up edge (BUE). In contrast, under LTUVSM conditions, the primary tool wear morphologies consist of chipping, adhesion, coating delamination, and crater wear. Furthermore, the dominant forms of tool wear under CSM conditions are adhesive wear, oxidative wear, abrasive wear, and diffusion wear, whereas under LTUVSM conditions, the main forms of tool wear comprise adhesive wear, oxidative wear, and diffusion wear.</p>