Due to their cost-effectiveness and ease of installation, smart wireless sensors have received considerable recent attention for structural health monitoring of civil infrastructure. Though various wireless smart sensor networks (WSSN) have been successfully implemented for full-scale structural health monitoring (SHM) applications, monitoring of low-level ambient strain still remains a challenging problem for wireless smart sensors (WSS) due to A/D converter resolution, inherent circuit noise, and the need for automatic operation. In this paper, the design and validation of high-precision strain sensor board for Imote2 WSS platform and its application to SHM of a cable-stayed bridge are presented. By accurate and automated balancing the Wheatstone bridge, signal amplification of up to 2507-times can be obtained. Temperature compensation and shunt calibration are implemented. In addition to traditional foil-type strain gages, the sensor board has been designed to accommodate a friction-type magnet strain sensor, facilitating fast and easy deployment. The sensor board has been calibrated using lab-scale tests, and then deployed on a full-scale cable-stayed bridge to verify its performance.