A comprehensive understanding of structure−activity relationships is beneficial for enabling the controlled synthesis of crystalline coordination polymers (CPs) with a macroscopic mechanical response. In this work, starting from a previously reported mechanically responsive CP material (U-CF 3 -phen) with a spine of triple-helix polymeric chains decorated by side-chain organic base ligands (1,10-phenanthroline, phen), two other new triple-helix CPs, U-CF 3 -bpy and U-CF 3 -dmbpy, that are isomorphic to U-CF 3 -phen were synthesized through side-chain engineering, i.e., replacing phen with two other organic base ligands, 2,2′-bipyridine (bpy) or 5,5′dimethyl-2,2′-bipyridine (dmbpy). Mechanical properties and thermochemical behaviors of these three analogues were characterized and systematically compared. The results show that U-CF 3 -bpy and U-CF 3 -dmbpy are both elastically bendable like U-CF 3 -phen, but have different elastic moduli and hardnesses, as revealed by the nanoindentation measurement. Besides its elastic nature, there is a difference in the thermal behavior of these compounds, and in particular, U-CF 3 -dmbpy does not even exhibit a thermosalient behavior. Potential energy surface analysis and variable-temperature single-crystal X-ray diffraction analysis are used to figure out the effect of side-chain groups on their mechanically responsive and thermosalient properties, which demonstrate that the regulation of side-chain groups from phen to bpy and then to dmbpy in these triple-helix CPs can lead to a gradual decrease in interchain π−π interactions but an increase in the steric hindrance and subsequently exert a significant influence on the apparent mechanical properties and thermosalient behaviors.