When undertaking long-distance missions at sea, vessels aim to achieve an extended operational range through drag reduction and energy efficiency, while enhanced wave resilience also provides substantial benefits. In this work, the Delft-372 catamaran is utilized to investigate the feasibility of drag reduction and roll mitigation for catamaran formation sailing in waves, analyzing the effects of three different formation configurations and varying spacings. The overset grid method was employed to simulate vessel motions, while the Volume of Fluid (VOF) method captured the free surface. First, the numerical results of the catamaran’s resistance, pitch, and heave motion amplitudes under different wave conditions were compared with experimental data to verify the accuracy of the CFD numerical method, and a grid convergence analysis was performed. Next, numerical models of the Delft-372 catamaran were constructed in parallel, tandem, and lateral formations under wave conditions. The results of the single-ship simulation were employed as a benchmark to analyze the impact of different formation configurations and varying lateral and longitudinal spacings on the resistance, pitch, and heave motions of the catamarans. The study also examined the effects of wave interference between vessels and the combined influence of external waves on individual and overall hydrodynamic performance. Results indicated that the tandem formation outperformed the parallel and lateral formations, with optimal performance observed at the longitudinal distance of 1 $L_{\mathit{PP}}$. Generally, during navigation, the follower catamaran should ideally be positioned in the trough of the stern wave of the leader catamaran.