Background: We aimed to investigate the association between contextual-level social determinants of health (SDoH) and the use of novel antidiabetic drugs (ADD), including sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1a) for patients with type 2 diabetes (T2D), and whether the association varies across racial and ethnic groups. Methods: Using electronic health records from the OneFlorida+ network, we assembled a cohort of T2D patients who initiated a second-line ADD in 2015–2020. A set of 81 contextual-level SDoH documenting social and built environment were spatiotemporally linked to individuals based on their residential histories. We assessed the association between the contextual-level SDoH and initiation of SGTL2i/GLP1a and determined their effects across racial groups, adjusting for clinical factors. Results: Of 28,874 individuals, 61% were women, and the mean age was 58 (±15) years. Two contextual-level SDoH factors identified as significantly associated with SGLT2i/GLP1a use were neighborhood deprivation index (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.81–0.94) and the percent of vacant addresses in the neighborhood (OR 0.91, 95% CI 0.85–0.98). Patients living in such neighborhoods are less likely to be prescribed with newer ADD. There was no interaction between race-ethnicity and SDoH on the use of newer ADD. However, in the overall cohort, the non-Hispanic Black individuals were less likely to use newer ADD than the non-Hispanic White individuals (OR 0.82, 95% CI 0.76–0.88). Conclusion: Using a data-driven approach, we identified the key contextual-level SDoH factors associated with not following evidence-based treatment of T2D. Further investigations are needed to examine the mechanisms underlying these associations.