Metal(loid)s can promote the spread and enrichment of antibiotic resistance in the environmental ecosystem through a co-selection effect. Little is known about the ecological effects of entering antibiotics into the environment with long-term metal(loid)s’ resistance profiles. Here, cow manure containing oxytetracycline (OTC) or sulfadiazine (SA) at four concentrations (0 (as control), 1, 10, and 100 mg/kg) was loaded to a maize cropping system in an area with high a arsenicals geological background. Results showed that exogenous antibiotics entering significantly changed the nutrient conditions, such as the concentration of nitrate nitrogen, ammonium nitrogen, and available phosphorus in the maize rhizosphere soil, while total arsenic and metals did not display any differences in antibiotic treatments compared with control. Antibiotics exposure significantly influenced nitrate and nitrite reductase activities to reflect the inhibition of denitrification rates but did not affect the soil urease and acid phosphatase activities. OTC treatment also did not change soil dehydrogenase activities, while SA treatment posed promotion effects, showing a tendency to increase with exposure concentration. Both the tested antibiotics (OTC and SA) decreased the concentration of arsenite and arsenate in rhizosphere soil, but the inhibition effects of the former were higher than that of the latter. Moreover, antibiotic treatment impacted arsenite and arsenate levels in maize root tissue, with positive effects on arsenite and negative effects on arsenate. As a result, both OTC and SA treatments significantly increased bioconcentration factors and showed a tendency to first increase and then decrease with increasing concentration. In addition, the treatments decreased translocation capacity of arsenic from roots to shoots and showed a tendency to increase translocation factors with increasing concentration. Microbial communities with arsenic-resistance profiles may also be resistant to antibiotics entering.