Mechanical microdrilling of nickel-based aerospace alloys suffers from premature drill breakage due to the fragile nature of the microdrill. Additionally, burr size reduction in both macro- and microscales has become one of the key problems in the drilling process. This paper presents a new method to microdrill Inconel 718 alloy using laser followed by mechanical drilling (sequential drilling). The aim of this research was to understand and evaluate the capability of using sequential laser mechanical drilling method as an effective and efficient method in drilling difficult-to-cut metals. Two new approaches were developed, namely, a two-step process of laser pilot drilling followed by twist drilling and a three-step process of laser pilot hole drilling followed by mechanical pilot drilling and then twist drilling. The holes produced by the new approaches were compared with those by mechanical microdrilling (pilot drilling and then twisting drilling). The results show that mechanical drilling eliminates the laser drilling defects. Furthermore, while large nonuniform burrs with attached cap were found in pure mechanical drilling, 75% reduction in burr size was achieved with the complimentary sequential drilling technology. Additionally, when compared with purely mechanical microdrilling, the new drilling method resulted in 240–430% tool life increase. Thus, the new drilling method presents an opportunity for industry to extend tool life and decrease burr.