Yaks have strong adaptability to extremely cold and hypoxic conditions but are susceptible to high ambient temperature when yaks are raised in low-altitude areas during the high-temperature season. Twenty-four adult male yaks with similar weights and ages were randomly divided into TN (Thermoneutral, altitude = 3464 m), LHS (Light heat stress, altitude = 1960 m), and MHS (Medium heat stress, altitude = 906 m) groups to evaluate adaptation strategies to HS. Non-targeted and targeted metabolomics were applied to investigate the effects of different extents of HS on yaks. LHS- and MHS-yaks showed higher rectal temperatures and respiratory rates than TN-yaks. MHS-yaks had higher levels of red blood cells (RBCs), hemoglobin (Hb), whole blood relative index of middle shear at a shear rate of 5 S-1 (WMS), whole blood relative index of high shear at a shear rate of 200 S-1 (WHS), Casson viscosity (CV), middle shear flow resistance at a shear rate of 5 S-1 (MSFR), and high shear flow resistance at a shear rate of 200 S-1 (HSFR) as compared to TN- and LHS-yaks. Differential metabolites and metabolic pathways, including fatty acid metabolism, lipid metabolism, glucose metabolism, and amino acid metabolism, were altered by HS. Metabolites in the glucose metabolism pathway in LHS- and MHS-yaks were lower than those in TN-yaks. However, LHS-yaks showed higher levels of metabolites in the HIF-1 signaling pathway compared to TN- and MHS-yaks. Most of the tricarboxylic acid cycle (TCA) intermediates and fatty acids were significantly decreased in MHS-yaks compared to the other two groups. As a whole, yaks raised at a low altitude (25.6 °C) suffered from severe HS, but they adapted to HS with vasodilatation for dissipating heat and the increased antioxidants and metabolite levels of energy substrates.