Methods and apparatus for isolation of sub-system resources (such as clocks, power, and reset) within independent domains. In one embodiment, each sub-system of a system has one or more dedicated power and clock domains that operate independent of other sub-system operation. For example, in an exemplary mobile device with cellular, WLAN and PAN connectivity, each such sub-system is connected to a common memory mapped bus function, yet can operate independently. The disclosed architecture advantageously both satisfies the power consumption limitations of mobile devices, and concurrently provides the benefits of memory mapped connectivity for high bandwidth applications on such mobile devices.