The present study focuses on understanding the structural dependence of sulfur (as SO3) solubility in Na2O–B2O3–SiO2 glasses over a broad composition space exhibiting a rich variety of structural associations. The focus is on probing the impact of the (1) structural role of Na+, (2) degree of polymerization, and (3) network former connectivity (formation of Si–O–B and B–O–B linkages) on sulfur solubility in borosilicate glasses. By employing a suite of state-of-the-art characterization techniques, including inductively coupled plasma-optical emission spectroscopy (ICP-OES), magic-angle spinning (MAS) NMR spectroscopy, and Raman spectroscopy, an inverse correlation has been established between the sulfur solubility and the degree of network polymerization in the glasses across the investigated composition space. While the modification of SO3 leading to the formation of SO42– can successfully compete with the network depolymerization mechanisms (i.e., creation of nonbridging oxygens) and induce repolymerization in the glass network, the BO3 → BO4 conversion facilitated by the charge compensation by alkali cations takes precedence. The results from this study, when extended to more complex borosilicate-based glass compositions, will not only add to our understanding of the fundamental science controlling the sulfur solubility in borosilicate-based real-world nuclear waste glasses but will also form a basis for the development of nonempirical quantitative structure–property relationship (QSPR)-based predictive models.