This study aimed to compare the acute effect of traditional (TR), cluster (CL), and rest redistribution (RR) set configurations on neuromuscular and perceptual measures of fatigue. Thirty-one resistance-trained men randomly performed a Control session and 3 experimental sessions consisting of the squat (SQ) and bench press (BP) exercises performed against the 10 repetition maximum load using TR (3 sets of 6 repetitions; 3 minutes of interset rest), CL (3 sets of 6 repetitions; 30 seconds of intraset rest every 2 repetitions; 3 minutes of interset rest), and RR (9 sets of 2 repetitions; 45 seconds of interset rest) set configurations. A significant effect of “set configuration” (p = 0.002) was observed for barbell velocity. The average velocity of the training session was lower for TR compared with CL (% difference = 5.09% in SQ and 5.68% in BP) and RR (% difference = 5.92% in SQ and 2.71% in BP). The 3 set configurations induced comparable decrements in countermovement jump height (% difference from −6.0% to −8.1%) and throwing velocity (% difference from −0.6% to −1.2%). Ratings of perceived exertion (RPE-10) values collected after the sets were higher for TR (SQ: 6.9 ± 0.7 a.u.; BP: 6.8 ± 0.8 a.u.) compared with CL (SQ: 6.2 ± 0.8 a.u.; BP: 6.4 ± 0.7 a.u.) and RR (SQ: 6.2 ± 0.8 a.u.; BP: 6.6 ± 0.9 a.u.), while the session RPE did not differ between the set configurations (p = 0.595). CL and RR set configurations allow for higher velocities and lower RPE values during resistance training sessions not performed to failure in comparison with a TR set configuration.