As antibiotic pollution from manured farmland soils has aroused public concern, their potential interaction with manure matrix/colloids especially manure-derived dissolved organic matter (DOM) often complicated their leaching behavior. This study investigated the leaching of sulfadiazine (SDZ), and florfenicol (FFC) in undisturbed field lysimeters of chickens-integrated orchard farmland under continuous natural rainfall events. Repacked column experiments were also conducted with manure-DOM treatments under soil matrix flow. The results indicate that manure presence could reduce SDZ mass flux, but the real-time migration may increase under favorable soil hydrological processes and heavy rainfall events. Whereas FFC was more prone to leaching in manured plot (0.48 µg m-2 h-1) as compared to the control (0.12 µg m-2 h-1), suggesting manure-DOM facilitated FFC leaching in field via a cotransport mechanism favored by abundant macropore flow in the soil. In contrast, SDZ and FFC’s mobility was reduced in repacked columns under manure-DOM conditions, suggesting increased adsorption, complexation and straining effects in soil matrix pores. Two kinetic site model and two-site nonequilibrium adsorption model fitted the breakthrough curves of SDZ and FFC well (0.988> r2 > 0.995 for SDZ and 0.973> r2 > 0.989 for FFC), revealing non-equilibrium conditions and kinetic sorption process in the repacked column. FFC exhibits lower leaching potential compared to SDZ in both column and field trials. Redundancy analyses revealed close relationship of FFC with humic-like components (C1 and C3), but SDZ is more related to protein-like component (C2) of manure-DOM. Therefore, as manure-DOM has a potential of increasing adsorption of highly mobile antibiotics on soil surface, however, scenario of macroporous soil under heavy rainfalls still leads to accelerated leaching. These findings highlight the combined impacts of manure-DOM and soil hydrological processes in modulating the ecological risks of antibiotics under natural conditions.