The nucleosome serves as the fundamental unit of chromatin organization, with electrostatic interactions acting as the driving forces in the folding of nucleosomes into chromatin. Perturbations around physiological pH conditions can lead to changes in the protonation states of titratable histone residues, impacting nucleosome surface electrostatic potentials and interactions. However, the effects of proton uptake or release of histone ionizable groups on nucleosome-partner protein interactions and higher-order chromatin structures remain largely unexplored. Here, we conducted comprehensive analyses of histone titratable residue pKa values in various nucleosome contexts, utilizing 96 experimentally determined complex structures. We revealed that pH-induced changes in histone residue protonation states modulated nucleosome surface electrostatic potentials and significantly influenced nucleosome-partner protein interactions. Furthermore, we observed that proton uptake or release often accompanied nucleosome-partner protein interactions, facilitating their binding processes. In addition, our findings suggest that alterations in histone protonation can also regulate nucleosome self-association, thereby modulating the organization and dynamics of higher-order chromatin structure. This study advances our understanding of nucleosome-chromatin factor interactions and how chromatin organization is regulated at the molecular level.