Despite many studies on ligand-modulated protein mechanics, a comparative analysis of the role of ligand binding site on any specific protein fold is yet to be made. In this study, we explore the role of ligand binding site on the mechanical properties of β-grasp fold proteins, namely, ubiquitin and small ubiquitin related modifier 1 (SUMO1). The terminal segments directly connected through hydrogen bonds constitute the β-clamp geometry (or mechanical clamp), which confers high mechanical resilience to the β-grasp fold. Here, we study ubiquitin complexed with CUE2-1, a ubiquitin-binding domain (UBD) from yeast endonuclease protein Cue2, using a combination of single-molecule force spectroscopy (SMFS) and steered molecular dynamics (SMD) simulations. Our study reveals that CUE2-1 does not alter the mechanical properties of ubiquitin, despite directly interacting with its β-clamp. To explore the role of ligand binding site, we compare the mechanical properties of the ubiquitin/CUE2-1 complex with that of previously studied SUMO1/S12, another β-grasp protein complex, using SMD simulations. Simulations on the SUMO1/S12 complex corroborate previous experimentally observed enhancement in the mechanical stability of SUMO1, even though S12 binds away from the β-clamp. Differences in ligand binding-induced structural impact at the transition state of the two complexes explain the differences in ligand modulated protein mechanics. Contrary to previous reports, our study demonstrates that direct binding of ligands to the mechanical clamp does not necessarily alter the mechanical stability of β-grasp fold proteins. Rather, binding interactions away from the clamp can reinforce protein stability provided by the β-grasp fold. Our study highlights the importance of binding site and binding modes of ligands in modulating the mechanical stability of β-grasp fold proteins.