Science education reformists in Thailand promote the use of socioscientific issues (SSIs)-based teaching to enrich scientific literacy for global citizenship. To achieve this goal, Thai pre-service science teachers (PSTs) must know how to effectively integrate SSIs into their science teaching practices. The purpose of this study was to enhance PSTs’ understanding and practices of SSIs-based teaching via the online mentoring (OM) program. Three PSTs were selected as case studies, and data were collected from online observations, semi-structured interviews, online discussions, and online document reviews. The analytical methods included within-case and cross-case analysis. This study found that the OM program was effective in enhancing PSTs’ understanding and practices of SSIs-based teaching. As a result, their teaching practices evolved from conveying content knowledge to promoting higher-order cognitive practices. In addition, the PSTs demonstrated a deeper appreciation for OM programs as a means to enhance teaching practices. This research demonstrates how the implementation of OM programs has the potential to be powerful tool for professional development of science educators, which is essential for transforming science educational practices.