Turbulent mixing layers associated with streamwise uniform and nonuniform flows in compound channels (main channel with adjacent floodplains) are experimentally investigated. The experiments start with uniform flow conditions. The streamwise nonuniformity is then generated by imposing an imbalance in the upstream discharge distribution between main channel (MC) and floodplains (FPs), keeping the total discharge constant, which results in a transverse depth‐averaged mean flow. This study first aims at assessing the effect of a transverse flow on the mixing layer and coherent structures that form at the MC/FP interfaces. A wide range of initial velocity ratio or dimensionless shear between MC and FP is tested. The study second aims at assessing the effect of this velocity ratio on the mixing layer, for a fixed vertical confinement of flow. The total discharge was then varied to quantify the confinement effect. The results show that, far from the inlet section, Reynolds‐stresses increase with local velocity ratio for a fixed confinement and decrease with confinement for a fixed velocity ratio. It is also shown that, irrespective of confinement, the existence of quasi‐two‐dimensional coherent structures is driven by velocity ratio and the direction and magnitude of transverse flow. These structures cannot develop if velocity ratio is lower than 0.3 and if a strong transverse flow toward the MC occurs. In the latter case, the transverse flow is the predominant contribution to momentum exchange (compared with turbulent mixing and secondary currents), convex mean velocity profiles are observed, preventing the formation of quasi‐two‐dimensional structures.