Recent experimental investigations of the photochemical properties of a series of sulfur-substituted pyrimidine derivatives provide insights into the phototherapeutic potential of these nucleobase variants. Herein we elucidate the triplet formation mechanism of two prospective UVA-activated phototherapeutic molecules, 4-thiothymine and 2,4-dithiothymine, upon photo-excitation by applying the trajectory surface hopping dynamics at the LR-TDDFT level. Our simulations reasonably reproduce the experimental time constants and demonstrate the preferred triplet formation pathway which starts from the S1(nSπ*) state for both molecules. It is found that deactivation of the first bright state to the S1(nSπ*) state proceeds through a mechanism involving elongation of the C5-C6 and C4-S8 bond-lengths and C2-pyramidalization in 4-thiothymine and involving elongation of the C5-C6 and C2-S7 bond-lengths in 2,4-dithiothymine. The intersystem crossing of 2,4-dithiothymine occurs either at geometries characterized by elongated C5-C6 and C2-S7 bond-lengths or at geometries showing elongated C5-C6 and C4-S8 bond-lengths as seen in 4-thiothymine. The solvents are found to affect the S2 state decay of 4-thiothymine, leading to a competing pathway between S2→ S1 and S2→ T3. This study provides a molecular-level understanding of the underlying excited-state relaxation of the two UVA-activated thiopyrimidines, which may be linked to their potential applications in pharmacological science and also prove helpful for designing more effective phototherapeutic agents.