Known for their exceptional magnetic properties, Sm-Co intermetallics often constitute the components of well-known permanent magnets. Specifically, SmCo₅ and Sm₂Co₁₇ represent two grades of Sm-Co magnets that offer high coercivity, thermal stability, and corrosion resistance. However, a fundamental understanding of the linkage between their lattice structures and deformation behavior remains elusive. In this study, we systematically investigated the slip systems in SmCo₂, SmCo₅, Sm₂Co₇, and Sm₂Co₁₇ using a combination of first-principles modeling and nanomechanical testing. Three active slip systems on the pyramidal (112 ̅1), prismatic (11 ̅01) and basal (0001) planes, detected in SmCo₅ through single-crystal nanoindentation and micropillar compression, were theoretically characterized. Generalized stacking fault energy and transition-state calculations revealed the favorability of such slip systems occurring in the more complex Sm₂Co₇ and Sm₂Co₁₇ lattices, which contain the SmCo₅ and SmCo₂ sublattices. The increase and decrease in the energy barriers of prominent slip systems, considering the influence of other building blocks in the complex crystals, were further examined. The results thus lay a foundation for understanding the deformation behavior of structurally related phases in the Sm-Co system.