Square steel tube, which is widely used in civil engineering, can suffer from a wide variety of damages and aging defects, thus its nondestructive testing (NDT) has attracted wide attention. This work proposes an ultrasonic guided wave (UGW)-based damage detection method for square steel tubes using structure symmetry. Firstly, the dispersion characteristics of square steel tubes are obtained using the semi-analytical finite element (SAFE) method, after which the optimal guided wave modes for damage located on the long and short edges of the steel tube are selected by modal analysis. Then, using the symmetry of the square steel tube’s section, the symmetric layout scheme of the transmitters and the receivers is designed; on this basis, a signal processing strategy for damage detection is proposed by subtracting the receiving signals obtained from symmetric positions. Finally, the effectiveness of the proposed damage detection method is verified by numerical simulations and laboratory experiments. The results show that the proposed method has good inspection accuracy for crack and hole damages on both the long and short edges of square steel tube because the dispersion effect and clutters can be reduced utilizing structure symmetry. It is worth mentioning that the inspection effect for corner holes can be enhanced by modifying the position of the receivers.