Organic wastes applied as composted amendments may improve the quality of degraded soils and modify the fate of pesticides. This work has set out to study the dissipation kinetics of the herbicides chlorotoluron and flufenacet during their second-year application in field experimental plots with a sandy-loam agricultural soil without amendment (S) and amended with spent mushroom substrate (S + SMS) or green compost (S + GC). The SMS and GC were applied to the soil during the previous winter’s wheat crop campaign (1 year before the second herbicide application) at rates of 140 and 85 t ha−1 (dry weight basis), respectively. The experiment involved randomized complete blocks with plots of 81 m2, including three replicates per soil treatment. Surface soils were sampled after herbicide application for 225 days, and herbicide residues in the soil samples were determined by HPLC-MS. The dissipation curves of both herbicides for the three soil treatments were better fitted to the first order multi-compartment (FOMC) kinetic model. The dissipation rates of the most hydrophobic herbicide, flufenacet, were slower than those for chlorotoluron in both unamended and amended soils. The half-life (DT50) values ranged between 20.7 to 41.1 days for chlorotoluron, and 42.9 to 75.6 days for flufenacet, and they followed the order S > S + SMS > S + GC. The DT50 values of chlorotoluron were close for S + SMS and S + GC, and the DT50 of flufenacet for S was similar to that for S + SMS. These DT50 values decreased up to four times with respect to those calculated after the first application indicating an accelerated dissipation of the herbicides after the second application especially in amended soil in comparison with unamended soil. The persistence of chlorotoluron and flufenacet in an agricultural soil was modified by the effect of the organic amendments, weather conditions, and possibly the repeated application of the compounds under real field conditions.