A bicycle wheel release mechanism can be configured to fit between dropouts on a bicycle. The release mechanism can have a ramp member and a ramp interface that rotate relative to one another to define a secured position where the wheel is secured to a bicycle and an open position where the wheel is releasable from the bicycle. The ramp member can be keyed to the bicycle such that the release mechanism can be operated or adjusted via single-handed operation. The ramp member can be configured with a variable angle ramp to facilitate rapid application for initial rotation of the mechanism followed by slower application as clamping forces increase when the release mechanism approaches the secured position.