In the present study, we explored the dynamics of antibiotics (ciprofloxacin, norfloxacin, enrofloxacin, and oxytetracycline), tetracycline resistance genes (TRGs), and bacterial communities over 2013-2015 in soils fertilized conventionally or with two levels (82.5 and 165 t/ha) of compost for 12 years. In the soil receiving 165 t/ha of compost, only oxytetracycline was 46% higher than that in the conventionally fertilized soil. Transient enrichment of both tetM (20% to 9-fold) and tetK (25% to 67-fold) was observed in multiple instances immediately after the application of compost. The majority of genera which positively correlated with tetM or tetK were affiliated to Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes. The structural equation model analysis indicated that fertilization regimes directly affected the bacterial composition and antibiotics and had an indirect effect on the abundance of tetK and tetM via these antibiotics. In summary, this study shed light into the complex interactions between fertilization, antibiotics, and antibiotic resistance pollution in greenhouse soil.