Moisture damage is a common distress in asphalt pavements caused by infiltrated moisture, which degrades mixture strength and affects pavement durability. Loaded wheel tracking (LWT) and modified Lottman (ML) tests are the two commonly used mechanical tests for assessing the moisture susceptibility of asphalt mixtures, but they have been reported to show limitations in consistently ascertaining the moisture sensitivity of different asphalt mixtures under field conditions. This study evaluated the effectiveness of different laboratory mechanical tests (LWT, ML, and semi-circular bend [SCB]) in ascertaining moisture sensitivity of asphalt mixtures. LWT, ML, and SCB tests were conducted on asphalt mixtures prepared with two asphalt binders (an unmodified PG 67-22 and a styrene-butadiene-styrene polymer-modified PG 70-22) and three aggregate types (limestone, crushed gravel, and semi-crushed gravel). Before testing, asphalt binder and mixture samples were exposed to five moisture conditioning levels: (1) unconditioned (dry), (2) single freeze-thaw cycle, (3) triple freeze-thaw cycle, (4) moisture induced stress tester (MiST) 3,500 cycles, and (5) MiST 7,000 cycles. A multiple stress creep recovery test was conducted on asphalt binders subjected to the five moisture conditioning levels. Results showed that the stress sensitivity of asphalt binders decreased after freeze-thaw and MiST conditioning. LWT rut depth and a new parameter which was developed as part of the study, SCB Jd ratio, were found to capture the progressive moisture damage in asphalt mixtures associated with different moisture conditioning levels. Mixtures containing PG 70-22 asphalt binder exhibited better moisture damage resistance compared with mixtures containing PG 67-22 asphalt binder.