Highly active MoS2 catalysts were developed by tuning the precursors and synthesis solvents to upgrade unconventional feedstocks into light fuels through the slurry-phase hydrogenation reaction. A highly dispersed quasi-single-layer (QSL) MoS2 nanocatalyst has been synthesized by the solvothermal method with L-cysteine and ethylene glycol as the S precursor and solvent, respectively. The QSL MoS2 nanocatalyst demonstrates extremely high selectivity to octahydroanthracene of 83.1% and hydrogenation percentage of 54.0% for catalytic anthracene hydrogenation, which are, respectively, 11.4 times and 2.6 times as high as those of bulk MoS2 catalysts. Moreover, the QSL MoS2 nanocatalyst exhibits excellent catalytic activities and high catalytic versatility for the slurry-phase hydrogenation of various unconventional feedstocks. The contents of light fractions (gas oil and diesel oil) in the hydrogenation products of coal tar and heavy crude oils from Boscana and Venezuela with the QSL MoS2 nanocatalyst are as high as 80%, and the conversion of asphaltene hydrogenation can reach much higher than 90%. The excellent catalytic activity of the QSL MoS2 nanocatalyst may result from its nanostructures including a grain size of 20-30 nm, QSLs of less than 3, and a slab length of 3-7 nm, which benefits to highly expose catalytic active sites and improve its dispersion in the slurry-phase hydrogenation reaction system. This synthesis method can be extended to the design of QSL two-dimensional materials with highly exposed active sites for various catalytic reactions.