Alkanes are the major constituents of natural gas and crude oil, the feedstocks for the chemical industry. The efficient and selective activation of C–H bonds can convert abundant and low-cost hydrocarbon feedstocks into value-added products. Due to the increasing global demand for light alkenes and their corresponding polymers as well as synthesis gas and hydrogen production, C–H bond activation of light alkanes has attracted widespread attention. A theoretical understanding of C–H bond activation in light hydrocarbons via density functional theory (DFT) and microkinetic modeling provides a feasible approach to gain insight into the process and guidelines for designing more efficient catalysts to promote light alkane transformation. This review describes the recent progress in computational catalysis that has addressed the C–H bond activation of light alkanes. We start with direct and oxidative C–H bond activation of methane, with emphasis placed on kinetic and mechanistic insights obtained from DFT assisted microkinetic analysis into steam and dry reforming, and the partial oxidation dependence on metal/oxide surfaces and nanoparticle size. Direct and oxidative activation of the C–H bond of ethane and propane on various metal and oxide surfaces are subsequently reviewed, including the elucidation of active sites, intriguing mechanisms, microkinetic modeling, and electronic features of the ethane and propane conversion processes with a focus on suppressing the side reaction and coke formation. The main target of this review is to give fundamental insight into C–H bond activation of light alkanes, which can provide useful guidance for the optimization of catalysts in future research.