Fatigue crack propagation mechanisms of bulk metallic glasses (BMGs) are not well understood, limiting their use in safety-critical structural applications particularly where complex fatigue loading may occur. Accordingly, the present study examines the effects of variable amplitude fatigue loading associated with block loading and tensile overloads on fatigue crack-growth rates in a Zr-based BMG. Crack growth studies were conducted on compact tension specimens using computer control of the applied stress intensity range, ΔK. Fatigue crack closure loads, which represent the initial contact of mating crack surfaces during the unloading cycle, were continuously monitored during testing. Abrupt drops in ΔK were found to significantly decrease fatigue crack-growth rates far below equilibrium values, arresting growth completely at a ΔK twice the nominal fatigue threshold ΔKTH. Conversely, an abrupt increase in ΔK was found to accelerate fatigue crack-growth rates. The effects of roughness-induced crack closure were assessed and found to be consistent with the suppression or acceleration of growth rates. However, in order to fully explain the observed transient growth rate response, other mechanisms that may be related to the fatigue mechanism itself were also considered. Specifically, the nature of the fatigue crack tip damage zone was also investigated. As BMGs lack distributed plasticity at low temperatures, the plastic zone differs greatly from that seen in ductile crystalline materials, and its role in fatigue crack propagation mechanisms is examined.