Tetracycline (TC) is a widely used antibiotic with a complex aromatic chemical structure and is highly resistant to biodegradation. In this study, an SBR equipped with a vertical axially rotating biological bed (SBR-VARB) was used for the biodegradation and mineralization of TC. SBR-VARB showed high efficiency in removing TC (97%), total phenolic compounds (TP) (95%), and COD (85%) under optimal operating conditions (TC = 50 mg/L, HRT = 1.75 d, and OLR = 36 g COD/m3d). The SBR-VARB was able to treat higher concentrations of TC in shorter HRT than reported in previous studies. The contribution of VARB to improve SBR efficiency in removing TC, TP, and COD was 16, 36, and 48%, respectively. Intermediate compounds formed during the biodegradation of TC were identified using GC–MS under the optimal operating conditions of the bioreactor. These are mainly organic compounds with linear chemical structures. Based on the complete biodegradation of TC under the optimal operating conditions of the bioreactor, 93% and 36% of the chlorine and nitrogen atoms in the chemical structure of TC appeared in the wastewater, respectively. According to the sequence analysis of 16SrDNA,Pseudomonassp.,Kocuria Polaris, andStaphylococcussp. were identified in the biofilm of VARB and the suspended biomass of the bioreactor. Therefore, SBR-VARB showed high efficiency in the biodegradation and mineralization of TC and can be used as a suitable option for treating wastewater containing antibiotics and other toxic compounds.