Systems, apparatuses, and methods for implementing a metadata tweak for channel encryption differentiation are disclosed. A memory controller retrieves a device-unique identifier (ID) from a memory device coupled to a given memory channel slot. The memory controller uses the device-unique ID to generate a tweak value used for encrypting data stored in the device. In one scenario, the device-unique ID is embedded in the address bits of the tweak process. In this way, the memory device can be migrated to a different memory channel since the data can be decrypted independently of the channel. This is possible since the device-unique ID used for the tweak operation is retrieved from the metadata stored locally on the memory device. In one implementation, the memory device is a persistent dual in-line memory module (DIMM). In some implementations, the link between memory controller and memory device is a compute express link (CXL) compliant link.