In this study, a comparison between ultrasonic-assisted drilling (UAD) and conventional drilling (CD) is presented under different feed rates using thrust force, torque, and hole geometrical errors as output responses. The experiments were done on plates of Inconel 601 (nickel-based superalloy), which is classified as a difficult-to-cut alloy due to its high Nickel content (60%), high hardness (43 HRC), and low thermal conductivity. The experiments were performed using DMG Mori Ultrasonic 20 linear, which is equipped with ultrasonic tool holderoscillating at 20 kHz with 7 μm amplitude. A coated carbide single margin twist drill had been used in the experiments. Full factorial design of experiments approach was employed, and the results had been statistically analyzed to find the most significant factor affecting the process responses. The results showed that the ultrasonic assistance had reduced the thrust force, and torque compared to conventional drilling (CD). Also, a reduction in holecylindricity error was detectedduring UAD, whichimprovesthe hole quality. In case of UAD, twist drills did not suffer from a physical wear, however notch wear was observed in CD drills. Chip morphology was also studied. Short segmented chips were obtained when using UAD which improved chip evacuation and reduced the chance of chip jamming in the drill flutes.