Due to the exceptional low density and high stiffness, cast Al-Li alloys are deemed suitable for structural applications. However, their economic benefits are limited by intolerable hot tearing susceptibility (HTS) during casting. This work aims to optimize alloy compositions that compromise low HTS and good mechanical properties. Six alloys (Alloys 1-6) with potentially high hot tearing resistance were selected by regulating Li, Cu and Mg additions based on the Kou′s criterion and ProCAST simulation. Experimental results indicated that in contrast to Alloys 1-4, Alloys 5 & 6 containing higher solute contents show anomalously high HTS, significantly deviating from the predictions. It was further revealed that this phenomenon originates from a variety of Li-rich inclusions formed at interdendritic channels, which lead to strain localization and hinder residual liquid refilling. Then, Alloys 1-4 with low HTS were subjected to a tailored subsequent heat treatment to achieve optimal mechanical properties. Among the tested alloys, Alloys 3 & 4 exhibit comparatively lower ductility attributed to strain accumulation at the interface between coalesced Sʹ-Al2CuMg phases and Al matrix. In comparison, a good combination of strength and ductility (YS = 371 ± 14 MPa, UTS = 456 ± 19 MPa, EL = 2.5 ± 0.1%) was successfully achieved in Al-2.5Li-2Cu-1Mg-0.15Zr alloy (Alloy 2) due to the synergistic reinforcement of δʹ-Al3Li and T1-Al2CuLi precipitates. Compared to other available cast Al-Li alloys, Alloy 2 possesses better hot tearing resistance while being highly competitive in strength. Our results are anticipated to contribute scientific guidance for developing high-performance cast Al-Li alloys with low HTS.