Understanding of anisotropy mechanism for Pilger rolling Ti80 (Ti-6Al-3 Nb-2Zr-1Mo) alloy pipe is of great significance to improve its service performance. In this work, the strength, plasticity and fracture mode of Ti80 alloy pipe with rolling texture in three different directions (RD, TD and 45°) were comparatively investigated. Firstly, the tensile strength is in the descending order of TD, RD and 45°, and plasticity shows the opposite trend. According to the statistics of a large number of deformed grains, the underlying mechanism of anisotropy was revealed by analyzing the slip activation, slip transfer, damage and fracture for three different loading directions. The results show that prismatic<a> slip is the dominant deformation mechanism in RD, and the basal<a> slip is mostly activated in TD. In 45°, the number of activated prismatic<a> slip and basal<a> slip is almost the same. Meanwhile, the pyramidal<a> slip plays an important role in accommodating the plastic deformation. A method for predicting the yield strength was established based on the critical resolved shear stress (CRSS) of basal<a> slip, prismatic<a> slip and pyramidal<a> slip, accompanying by different SFs distributions of activated slip systems. Subsequently, slip transfer, which can relieve the incompatible deformation, occurred between adjacent α grains when the slip transfer factor (m) and Schmidt factor (SF) are at a high value. Slip transfer was prone to occurring between the same slip systems, such as between prismatic<a> slip or basal<a> slip. However, it is discovered that the slip transfer between prismatic<a> slip and basal<a> slip is also likely to occur, when the adjacent α grains maintain 90° variant relationship. The slip transfer between 90° variants in 45° have higher probability than that in RD and TD due to high SFs of activated basal<a> slip and prism<a> slip, resulting better plasticity. Lastly, the micro-defects are uniformly distributed and the fracture mode is microvoids coalescence in RD. More basal<a> slip induces the cleavage cracks and cause the shear fracture in 45°. In TD, a mixed fracture mode of microvoids coalescence and cleavage is presented due to the heterogeneous deformation.