To study the effects of micro-groove cross section asymmetry on the flow characteristic and drag reduction efficiency under rotation, numerical simulations of various rotating disks with micro-grooves were performed. Experiments of two representative disks were conducted for comparison and validation. Both numerical results and experimental results show that micro-grooves are effective in drag reduction. The fluid flow is promoted at one micro-groove sidewall and suppressed on the other side. There is an extended low-pressure area between the micro-grooves and the disk clearance, which demonstrates the interaction phenomenon exists, could be discovered. The interaction phenomenon makes the micro-groove fluid suppress the clearance fluid. When the disks rotate, the micro-groove fluids are suppressed, and the extended low-pressure areas are intensified overall. Positive asymmetry coefficient micro-grooves have larger high-pressure areas, and negative asymmetry coefficient micro-grooves have larger low-pressure areas. A higher asymmetry coefficient micro-groove has a greater asymmetrical pressure distribution. In contrast, the extended low-pressure areas are slightly affected by micro-groove geometries. Positive asymmetry coefficient micro-grooves, including zero asymmetry coefficient micro-grooves, have higher drag reduction efficiencies, whereas negative asymmetry coefficient micro-grooves have lower drag reduction efficiencies. The optimal micro-groove asymmetry coefficient is 0.25–0.5 within the rotating Reynolds number limits of 0.703 × 106–1.406 × 106.