One of the most industrially affected rivers in Taiwan, the Houjing River, was studied in this research. The water and sediment samples were collected at five locations to measure the concentration of eight metals (As, Cd, Cr, Cu, Hg, Pb, Ni, and Zn). In order to assess the heavy metal contamination and its adverse biological effect, the heavy metal pollution index (HPI), the degree of contamination index (DC), the contamination factor (CF), the index of geo-accumulation (I), and hazard quotients (HQs) were employed. The results showed that the Houjing River's water and sediment were contaminated with heavy metals. The annually averaged values of HPI (128.3) and DC (21.3) indicate that the water is unsafe for potable use and the sediment contamination level is at considerable degree of contamination. CF and I calculation show that Zn, Cu, and Cd are the three main metals contributing to heavy metal contamination in sediment. Evaluation of adverse biological effects suggests that Zn, Cu, and Ni are the major metals that cause adverse effects on organisms. This study provides an overview of the synergistic heavy metal contamination degree of the Houjing River and its adverse biological effects, which should be a reliable reference for future contamination control and management plans.