Trailing edge loss typically accounts for a third of the profile loss of a transonic turbine blade. In this paper, two dominant influencing factors—boundary layer state and trailing edge wedge angle—are quantified using a combined experimental (single airfoil transonic tests) and computational (wall-resolved LES) approach. Three key findings are reported. First, the switch between two flow regimes—detached vortex shedding and transonic vortex shedding—as the Reynolds number is increased, is identified and explained. It is shown that the transition of the pressure surface boundary layer drives the switch from the former to the latter; this change is associated with a jump in loss of close to 100%. The switch is also shown to affect the base pressure distribution around the trailing edge, changing it from uniform, with an isobaric dead-air region, to non-uniform. Second, the influence of the trailing edge wedge angle is explored. It is found that higher wedge angles can offer performance benefits in both loss and base pressure—with a change from 8 deg to 14 deg geometry providing up to a 29% reduction in an overall loss for the geometry tested. Finally, as these findings are the result of changes to the unsteady flow phenomena around the trailing edge, they would not be picked up by current low-fidelity, steady design tools. A method is proposed to use data, such as that presented in this paper, to improve low-fidelity modeling.