An electronic device may be provided with wireless circuitry. Control circuitry may be used to adjust the wireless circuitry. The wireless circuitry may include an antenna that is tuned using tunable components. The control circuitry may gather information on the current operating mode of the electronic device, sensor data from a proximity sensor, accelerometer, microphone, and other sensors, antenna impedance information for the antenna, and information on the use of connectors in the electronic device. Based on this gathered data, the control circuitry can adjust the tunable components to compensate for antenna detuning due to loading from nearby external objects, may adjust transmit power levels, and may make other wireless circuit adjustments.