Currently, two-dimensional imaging technology is the main approach adopted to characterize the particle shape of manufactured sand, while the morphological parameters measured in this way are different from the actual shape of particles, thus it cannot accurately reflect the particle shape, and causes errors in the mix proportion design of manufactured sand and the prediction of slurry flowability. In this paper, based on CT scanning technology, four types of manufactured sand and river sand samples with different lithologic features were scanned three-dimensionally, to obtain five key morphological parameters of the samples. By the entropy method, different weights were given to five key morphological parameters through nondimensionalization and proportional distribution, to obtain the comprehensive morphological parameters of manufactured sand. The comprehensive morphological parameters of five different lithologic manufactured sand samples were studied, and the flowability of gap-graded (0.6 ∼ 1.18 mm) and continuously-graded (0 ∼ 4.75 mm) manufactured sand mortars with different volume fractions was systematically investigated. The research results show that: CT scanning can accurately reconstruct the real three-dimensional morphology of the sand particles and precisely calculate the three-dimensional morphological parameters such as sphericity, roughness, shape factor, aspect ratio and flatness of granite, tuff, basalt and limestone manufactured sand and river sand samples. Entropy method was exploited to obtain the comprehensive morphological parameters of manufactured sand samples according to the numeric features of different morphological parameters. Based on the proposed comprehensive morphology parameters and the traditional Chateau model, a rheological model of yield stress of manufactured sand mortar considering comprehensive morphological parameters was established. Compared with the experimental results, it is found that the proposed model can more accurately predict the flowability of manufactured sand mortar. Finally, the influencing mechanism of different comprehensive morphological parameters on the flowability of manufactured sand mortar was revealed by using the excess paste theory.