Background/Objectives: Minimally invasive surgical techniques require precise psychomotor skills distinct from those used in traditional surgery. Simulation-based training is essential for skill acquisition without patient risk. This study compared two prevalent training methodologies: the Origami-Box-Folding Exercise (OBFE) and Outside-the-Box Knot-Tying Exercise (OBTKE). Methods: In this prospective cohort study, 84 surgical residents (34 OBFE, 50 OBTKE) from General Surgery, Obstetrics–Gynecology, and Urology underwent pre- and post-intervention assessments. Performance metrics included completion times for surgical and square knots, out-of-visual-field instrument instances, needle drops, tissue lesions, and self-assessment via 5-point Likert scales. Behavioral Observation Research Interactive Software quantified performance objectively. Data were analyzed using paired Wilcoxon signed-rank tests for within-group comparisons and Wilcoxon rank-sum tests for between-group differences. Results: Both methodologies significantly improved surgical knot-tying performance. Surgical knot completion time decreased by 316.65 s (OBFE) and 360 s (OBTKE) with no significant between-group difference (p = 0.96). For square knots, OBFE exhibited significantly greater improvement with a 278 s reduction versus 169 s for OBTKE (p = 0.02). Technical errors decreased similarly in both groups. OBFE showed greater improvement in self-rated surgical knot knowledge (p = 0.03) and larger effect sizes for self-assessment measures (0.84–0.87 vs. 0.77–0.85). Conclusions: Both OBFE and OBTKE effectively improve laparoscopic skills in surgical residents. OBFE is particularly beneficial for square knot efficiency and self-rated knowledge enhancement, while OBTKE focuses on targeted knot-tying training. These findings support the implementation of both methodologies in surgical education, potentially in sequence—OBFE for foundational skills and OBTKE for advanced refinement.