Systems and methods for enabling one-handed gesture sequences in virtual, augmented, and mixed reality (xR) applications are described. In an illustrative, non-limiting embodiment, an Information Handling System (IHS) may include a processor and a memory coupled to the processor, the memory having program instructions stored thereon that, upon execution, cause the IHS to: receive a gesture sequence from a user wearing a Head-Mounted Device (HMD) coupled to the IHS, where the HMD is configured to display an xR application; identify the gesture sequence as a one-handed sequence; and execute a command in response to the one-handed sequence.