The U-duct turbulent flow is a known benchmark problem with the computational challenges of high Reynolds number, high curvature and strong flow dependence on the inflow profile. We use this benchmark problem to test and evaluate the Space–Time Variational Multiscale (ST-VMS) method with ST isogeometric discretization. A fully-developed flow field in a straight duct with periodicity condition is used as the inflow profile. The ST-VMS serves as the core method. The ST framework provides higher-order accuracy in general, and the VMS feature of the ST-VMS addresses the computational challenges associated with the multiscale nature of the unsteady flow. The ST isogeometric discretization enables more accurate representation of the duct geometry and increased accuracy in the flow solution. In the straight-duct computations to obtain the inflow velocity, the periodicity condition is enforced with the ST Slip Interface method. All computations are carried out with quadratic NURBS meshes, which represent the circular arc of the duct exactly in the U-duct computations. We investigate how the results vary with the time-averaging range used in reporting the results, mesh refinement, and the Courant number. The results are compared to experimental data, showing that the ST-VMS with ST isogeometric discretization provides good accuracy in this class of flow problems.