A fluid infusion device and related operating methods are disclosed. The fluid infusion device has a housing, a fluid pump mechanism having an inlet and an outlet, a first flow path in fluid communication with the inlet and at least partially defined by structure compatible with fluid cartridge modules containing medication fluid, a second flow path in fluid communication with the outlet and terminating at a subcutaneous conduit for a body, and a drive motor that actuates the pump mechanism. An exemplary operating method detects a first installation of a fluid cartridge module in the housing. The detecting occurs after the housing has been affixed to the body and after the subcutaneous conduit has been inserted into the body. In response to the detecting, the operating method initiates an automatic priming operation to prepare the device for delivery of the medication fluid to the body.