Periodical relining of the gasifier due to refractory corrosion and failure is a major cost driver in the coal gasification industry. In the present work, the failure mechanisms of Cr2O3-Al2O3-ZrO2 refractory bricks taken from different areas of an industrial opposed multi-burner (OMB) gasifier were investigated by post-mortem analysis. The results demonstrated that a densified (Mg, Fe)O-n(Al, Cr)2O3 complex spinel layer was attained on surface of refractory, which inhibited the further infiltration of slag. The SiO2 and CaO in slag were the main corrosive components and infiltrated into the refractory through pores and cracks. Damage of used bricks was mainly due to crack growth as well as structural spalling caused by different thermal expansion coefficient of de-zirconium layer, infiltration layer and original brick layer. In addition, the failure mechanisms of refractory bricks in different areas were also different owing to unique flow field and structure of OMB gasifier. The dome brick has the smallest wear, which was mainly destroyed by thermal corrosion, the strong scouring of upward flow unit and folded back flow unit. The sidewall brick was damaged by the scouring of high-speed airflow, chemical corrosion and high temperature creep. The damage of lower cone brick was mainly caused by strong mechanical scouring and structural spalling, which has the shortest service life.