In surface waters, photodegradation is a major abiotic removal pathway of the neurotoxin monomethylmercury (MMHg), acting as a key control on the amounts of MMHg available for biological uptake. Different environmental factors can alter the rate of MMHg photodegradation. However, our understanding of how MMHg photodegradation pathways in complex matrixes along the land-to-ocean aquatic continuum respond to changes in salinity, dissolved organic carbon (DOC) concentration and dissolved organic matter (DOM) composition is incomplete. In a set of laboratory experiments combining several artificial and natural waters, we demonstrate that the interplay of DOC concentration, DOM composition, and salinity affects the photodegradation rate of MMHg. The presence of DOM was found to facilitate MMHg photodegradation, but degradation rates were not altered by varying DOC concentrations over two orders of magnitude. We found DOM composition to have a stronger effect on MMHg photodegradation rates than DOC concentration. However, at high DOC levels, where most UV radiation was lost within the first cm of the reaction vessels, lower MMHg photodegradation rates were observed. When moving from terrestrially influenced waters, characterized by a high degree of humification, towards marine conditions with a protein-rich DOM pool, MMHg photodegradation rates increased. In contrast, salinity had a stabilizing effect on MMHg. Hence, especially in systems with low salt and DOC concentrations, changes in either salinity or DOC concentration can impact the photodegradation rates of MMHg.