Tetracycline antibiotics (TCs) introduced into agricultural fields via manure application tend to accumulate in soils and further reach water environments via surface runoff and leachate, posing potential risks to regional water environment. This study investigated the loss of tetracycline (TC), oxytetracycline (OTC), and chlortetracycline (CTC) in surface runoff and leachate samples collected from a vegetable farmland with manure application in Guangzhou, South China. A risk assessment method was constructed for evaluating the ecological and health risks of manure-associated antibiotics released from soil into water environment. The results showed that the concentrations of three TCs in surface runoff, 30-cm leachate, and 60-cm leachate after the first rainfall event were 2.79–35.97, 1.71–18.44, and 0.4–2.66 μg/L, respectively, which all decreased with sampling depth and the time after rainfall events. Up to 0.13% of TCs were transported into the surface water through surface runoff, while less than 0.01% of TCs were transported into the groundwater through leachate at 60 cm. OTC had a higher total mass percentage (0.13%) into surface water via runoff than CTC (0.11%) and TC (0.07%) likely due to its smallest Kd value and largest input mass. Based on loss percentages, their predicted environmental concentrations (PEC) ranged from 4.87 (TC) to 16.91 (OTC) ng/L in regional surface water and 1.42 (TC) to 5.20 (CTC) ng/L in regional groundwater. The risk assessment based on PEC results suggested non-negligible health risk (HQ > 1.0 × 10−6) and low ecological risk (RQ < 0.1) in both regional surface water and groundwater, drawing concerns on the potential hazards of TCs released from manure-amended soil into water environments.