Aqueous photolysis of clethodim herbicide in the presence of natural substances such as humic acids (HA), nitrate, and Fe(III) ions has been investigated. The photodegradation rate of clethodim was retarded in the presence of HA compared to ultrapure water, while nitrate ions had no effect. On the other hand, water containing different concentrations of Fe(III) ions enhanced degradation of this herbicide. Clethodim transformation gave rise to the formation of nine byproducts, some of them, to the best of our knowledge, described for the first time in this work. The identification of these photoproducts has been accomplished by coupling liquid chromatography to quadrupole time-of-flight mass spectrometry. The main transformation reactions observed for clethodim were photoisomerization to the Z-isomer, S-oxidation of E- and Z-clethodim isomers giving rise to sulfoxide diastereoisomers, reduction of the oxime moiety to yield clethodim imine, oxidative cleavage of the C-S bond, and S-oxidation of clethodim imine leading to the formation of imine ketone and imine sulfoxide.