<p>This study investigates the influence of three innovative drilling kinematic systems on the quality of through-holes made in CuZn40Pb2 brass alloy. The focus is on two critical output parameters: hole straightness deviation (STRₜ) and surface roughness (Ra). Drilling tests were performed using 27 combinations of spindle speed, feed per revolution, and drilling kinematic variant. The experiments were conducted on a CNC turning center using internal coolant-supplied carbide drills. Statistical methods including ANOVA and response surface methodology (RSM) were used to assess factor significance and develop predictive models. The results show that the drilling variant had the highest influence on both quality indicators, with contribution ratios of 60.92% for STRₜ and 61.25% for Ra. The first drilling concept, where the tool performs both rotary and feed motion while the workpiece remains fixed, produced the most favorable outcomes with the lowest average Ra (compared to the second concept, the drillings are 29% smaller, compared to the third by 18%). In contrast, the second drilling concept, in which it is the workpiece that performs rotary motion and the tool performs only reciprocating motion, gave the most favorable results with the lowest average value of hole straightness (compared to the first concept by 36%, compared to the third by 28%). Regression models achieved high accuracy (<i>R</i>² &gt; 0.80), supporting their use for process optimization. The findings confirm that drilling kinematics significantly affect machining accuracy and can be optimized to enhance hole quality in precision brass component manufacturing.</p> Graphical Abstract <p></p>