In the present study, a series of conventional triaxial tests (CTTs) and true triaxial tests (TTTs) were performed on sandstone through a self-developed true triaxial testing system, which was combined with acoustic emission (AE) monitoring and X-ray computed tomography (CT) scanning technique to systematically study the damage and failure behavior of sandstone in different triaxial stress states. The results show that the damage evolution process of the specimen under the CTT and TTT conditions could be divided into four stages based on the AE monitoring observations: microcrack closure, stable growth of microcracks, unstable growth of microcracks, and post-peak phase. During the first three stages, the spatial-temporal distribution of the AE activity under the two loading conditions was nearly equal. However, in the post-peak stage, abrupt changes in the AE locations occurred more often under the CTT conditions than under the TTT conditions. The overall AE activity under the CTT conditions decreased with increasing confining pressure, whereas under the TTT conditions, it tended to strengthen first and then weaken with increasing intermediate principal stress. The post-test CT scanning observations show that the fracture morphology of the specimen under the TTT conditions was more regular and simpler than that under the CTT conditions. The fracture surface area of the specimen under the CTT conditions tended to decrease with increasing confining pressure, whereas that of the specimen under the TTT conditions tended to decrease first and then increase with increasing intermediate principal stress.