A 3-yr field study quantified leaching and runoff losses of antibiotics from land application of liquid hog (chlortetracycline and tylosin) and solid beef (chlortetracycline, monensin, and tylosin) manures under chisel plowing and no-tillage systems. The study was conducted in southwestern Wisconsin, a karst area with steep, shallow, macroporous soils. Relative mass losses of chlortetracycline, monensin, and tylosin were <5% of the total amount applied with manure. Chlortetracycline was only detected in runoff, whereas monensin and tylosin were detected in leachate and runoff. Highest concentrations of monensin and tylosin in the leachate were 40.9 and 1.2 μg L-1, respectively. Highest chlortetracycline, monensin, and tylosin concentrations in runoff were 0.5, 57.5, and 6.0 μg L-1, respectively. For all three antibiotics, >90% of detections and 99% of losses occurred during the non-growing season due to fall manure application and slow degradation of antibiotics at cold temperatures. During years of high snowmelt, runoff accounted for nearly 100% of antibiotic losses, whereas during years of minimal snowmelt, runoff accounted for approximately 40% of antibiotic losses. Antibiotic losses were generally higher from the no-tillage compared with chisel plow treatment due to greater water percolation as a result of macroporosity and greater runoff due to lack of surface roughness in the no-tillage plots during the non-growing season. The results from this study suggest that small quantities of dissolved antibiotics could potentially reach surface and ground waters in the Upper Midwestern USA from manure-amended shallow macroporous soils underlain with fractured bedrock.