This paper presents a wireless bio-signal acquisition system-on-chip (WBSA-SoC) that is specialized in electrocardiogram (ECG) monitoring. The proposed system comprises the design and implementation with three subsystems, namely, (1) the ECG acquisition node, (2) the protocol for standard IEEE 802.15.4 ZigBee system, and (3) the radio frequency (RF) transmitter circuits. A preamplifier circuit with a differential difference amplifier (DDA) structure, a 4th Butterworth low-pass filter (LPF), and a successive- approximation analog-to-digital converter (SA-ADC) are integrated to acquire an ECG signal. For high integration, applicability, and portability, the ZigBee protocol is adopted for wireless communication. A fully integrated CMOS RF front-end contains a quadrature voltage-controlled oscillator (QVCO) and a 2.4 GHz low-IF transmitter with a power amplifier and an up-conversion mixer, which is employed to transmit the ECG signal through wireless communication. The low-power wireless bio-signal acquisition SoC has been implemented in TSMC 0.18-μm standard CMOS process. The measurement results on the human body reveal that the ECG signals can be acquired effectively by the proposed SoC.