Excellent hole quality is necessary for the aerospace industry’s highly abrasive carbon fiber reinforced polymer (CFRP) drilling process. This work considered three different twist drill designs, tapered web, burnishing, and subland drill reamer for the drilling process. The drill bits were made of tungsten carbide and machined with custom helix angle, primary clearance, point angle, and chisel angle. The primary objective of this research is to determine the thrust force signature for each custom drill bit design and the delamination factor for the hole drilling at 3000 rev/min and 0.05 mm/rev. The finding indicates that the tapered web gave the best design by improving the maximum thrust force by 14.6% in drilling CFRP panels. Additionally, the tapered web design led to a low delamination factor on both entrance (1.0186) and exit sides (1.0475). The thrust force is directly proportional to the delamination factor when drilling a CFRP material in a single shot operation. The subland drill reamer produces higher thrust force, and delamination proved that the combination of drill and reamer design was unsuitable for high-speed drilling.