An exemplary method for using USB device descriptors to uniquely identify computing environments may include: 1) detecting a set of USB devices connected to a computing device within a computing environment, 2) obtaining a USB device descriptor for each USB device within the set of USB devices, and then 3) creating an environmental signature for the computing environment that identifies the computing environment based at least in part on the USB device descriptors. Exemplary methods for using such environmental signatures to uniquely identify computing environments are also disclosed.