With the large-scale development of livestock and poultry breeding industry, large amount of livestock and poultry manure has been used to agriculture, resulting in the deterioration of combined pollution of heavy metals and antibiotics in soil. In this paper, the feed additives copper (Cu) and sulfadiazine (SDZ), which are commonly used in livestock and poultry breeding, were used as the target pollutants. The soil enzyme kit (micro method) and Biolog ECO-plate method were adopted to study the effect of the combined pollution on enzyme activity and the functional diversity of soil microbial community. The results showed that low concentration of Cu (200 mg/kg) combined pollution could alleviate the inhibitory effect of SDZ on soil dehydrogenase and β-glucosidase, i.e., antagonistic effect. However, SDZ had a synergistic inhibitory effect on phosphatase. The high concentration of Cu (500 mg/kg) and SDZ complex showed synergistic inhibition on soil enzymes tested. Biolog ECO-plate analysis showed that the addition of 10 mg/kg SDZ promoted soil microbial activity, while the combination of Cu and SDZ significantly inhibited soil microbial metabolic activity. The diversity index analysis showed that the combined pollution of Cu and SDZ had little effect on microbial community traits, but significantly changed the homogeneity of microbial populations. Principal component analysis also showed that the combined pollution could significantly change soil microbial community structure. In conclusion, the effect of Cu and SDZ combined pollution on soil enzyme activity is related to soil enzyme species and pollutant concentration, and soil dehydrogenase is a sensitive indicator reflecting SDZ and its combined pollution with Cu; The combined pollution of Cu and SDZ can significantly inhibit the overall metabolic activity of soil microbial communities and change the metabolic function, thus can promote the changes of soil microbial structure.