The aquatic photochemical behavior of a class of sulfa drugs containing six-membered heterocyclic substituents (sulfamethazine, sulfamerazine, sulfadiazine, sulfachloropyridazine, and sulfadimethoxine) was investigated. Photodegradation of the sulfa drugs in a natural water sample was significantly enhanced relative to the degradation in deionized water, with the exception of sulfadimethoxine. This indicated an indirect photochemical process that was identified through the use of quenchers to be attributable to interaction with triplet excited-state dissolved organic matter (3DOM). The direct photolysis rate constant and quantum yield for both the neutral and anionic species of each sulfa drug were calculated using matrix deconvolution methods. The quantum yield values range from 0.01 × 10-3 for the neutral form of sulfadimethoxine to 5 × 10-3 for the anionic form of sulfamethazine and are significantly lower than those observed in a previous study for sulfa drugs containing five-membered heterocyclic substituents, although the rate constants are of similar magnitude. The primary product formed in both direct and indirect photodegradation for all five compounds was identified as a sulfur dioxide extrusion product. The predicted environmental half-lives solely attributable to direct photolysis range from 8.6 h in midsummer at 30° latitude in pH 7 surface water for sulfachloropyridazine to 420 h in midwinter at 45° in pH 7 surface water for sulfadimethoxine. These half-lives, except for sulfadimethoxine, will be decreased by interaction with 3DOM.