A two-layer model for predicting the vertical distribution of stream-wise velocity in open channel flow with submerged flexible vegetation is proposed. Using the predicted deflection height of the flexible vegetation determined via the large-deflection cantilever beam theory, the flow is vertically separated into a bottom vegetation layer and an upper free water layer, and corresponding momentum equations for each layer are formulated. In the bottom vegetation layer, the resistance caused by the deflected plants is calculated accounting for plant bending rather than adopting the existing resistance formula for erect rigid vegetation. For the upper free water layer, a new type of polynomial velocity distribution is suggested instead of the traditional logarithmic velocity distribution to obtain a zero velocity gradient at the water surface. To validate the proposed model, the published experimental data are employed.