Double-transition-metal MXenes (D-MXenes) have been widely pursued in the advancement of the renewable energy storage technology in recent years. In this work, the hydrogen evolution reaction (HER) catalytic mechanism of several oxygen-terminated D-MXenes with the chemical formula of M’2M″C2O2 (M’ = Mo, Cr; M″ = Ti, V, Nb, Ta) is theoretically studied. For comparison, the corresponding monometallic MXenes (M-MXenes, M’3C2O2) are fairly compared by means of the density functional theory calculations. Based on our theoretical results, the HER performance of M-MXenes can be improved by constructing a “sandwich-like” ordered D-MXene configuration. Moreover, the HER performance of Mo-based D-MXenes (Mo2M″C2O2) is superior to that of Cr-based D-MXenes (Cr2M″C2O2), which highlights that the HER activity of Mo2VC2O2 and Mo2NbC2O2 is better than that of Pt(111). This work not only unravels the HER mechanism of D-MXenes (M’2M″C2O2) but also paves the way in designing emergent MXene-based HER electrocatalysts with high efficiency.