Portable electronic devices are provided with wireless circuitry. The wireless circuitry may include one or more sets of radio-frequency power amplifiers. The radio-frequency power amplifiers are used to amplify radio-frequency signals that are transmitted by the portable electronic devices. Each power amplifier may have multiple gain mode settings. Gain stages within the power amplifiers may be selectively enabled in accordance with the gain mode settings. When a higher level of gain is required, all of the gain stages may be enabled. When a lower level of gain is required, some of the gain stages may be disabled to conserve power. An adjustable power supply may be used to provide an adjustable power supply voltage to the power amplifiers. The adjustable power supply voltage can be reduced when it is desired to minimize power consumption at a particular gain mode setting. Gain mode and power supply settings may be adjusted simultaneously.