To improve the heat resistance of titanium alloys, the effects of Y content on the precipitation behavior, oxidation resistance and high-temperature mechanical properties of as-cast Ti-5Al-2.75Sn-3Zr-1.5Mo-0.45Si-1W-2Nb-xY (x = 0.1, 0.2, 0.4) alloys were systematically investigated. The microstructures, phase evolution and oxidation scales were characterized by XRD, Laser Raman, XPS, SEM and TEM. The properties were studied by cyclic oxidation as well as room- and high-temperature tensile testing. The results show that the microstructures of the alloys are of the widmanstätten structure with typical basket weave features, and the prior β grain size and α lamellar spacing are refined with the increase of Y content. The precipitates in the alloys mainly include Y2O3 and (TiZr)6Si3 silicide phases. The Y2O3 phase has specific orientation relationships with the α-Ti phase: (002)Y2O3 // (1¯1¯20)α-Ti, [110]Y2O3 // [4¯401]α-Ti. (TiZr)6Si3 has an orientation relationship with the β-Ti phase: (022¯1¯)(TiZr)6Si3 // (011)β-Ti, [1¯21¯6](TiZr)6Si3 // [044¯]β-Ti. The 0.1 wt.% Y composition alloy has the best high-temperature oxidation resistance at different temperatures. The oxidation behaviors of the alloys follow the linear-parabolic law, and the oxidation products of the alloys are composed of rutile-TiO2, anatase-TiO2, Y2O3 and Al2O3. The room-temperature and 700 °C UTS of the alloys decreases first and then increases with the increase of Y content; the 0.1 wt.% Y composition alloy has the best room-temperature mechanical properties with a UTS of 1012 MPa and elongation of 1.0%. The 700 °C UTS and elongation of the alloy with 0.1 wt.% Y is 694 MPa and 9.8%, showing an optimal comprehensive performance. The UTS and elongation of the alloys at 750 °C increase first and then decrease with the increase of Y content. The optimal UTS and elongation of the alloy is 556 MPa and 10.1% obtained in 0.2 wt.% Y composition alloy. The cleavage and dimples fractures are the primary fracture mode for the room- and high-temperature tensile fracture, respectively.