Eight pharmaceuticals and personal care products (PPCPs), two sulfonamide resistance genes, and nine heavy metals were quantified in surface sediments collected from Chao Lake, China. The results showed that methylparaben and bisphenol A were predominant among the selected PPCPs, being found in concentrations of (1.35 ± 0.31)–(5.20 ± 0.79) and (0.68 ± 0.19)–(4.82 ± 1.21) ng g−1, respectively. Quantitative real-time PCR revealed that the sulfonamide resistance genes sul1 and sul2 were present in all sediment samples, with the absolute abundance ranging from (1.18 ± 0.03) × 106 to (6.90 ± 0.12) 108 copies g−1. Modified potential risk assessment methodology analysis of available test data demonstrated that Chao Lake is exposed to moderate, considerable, or very high ecological risk and that Cd and Hg were the priority pollutants of greatest concern. Positive correlation (p < 0.01 or p < 0.05) was found between certain heavy metals (such as Zn and Cd, As and Cd), whereas Cr and Ni displayed a negative correlation. A significant positive correlation was observed between sul1 and sul2 (p < 0.01), as well as between TOC and sul1 and TOC and sul2 (p < 0.05), whereas no significant correlations were found between these genes and individual heavy metals. Overall, this study confirmed the presence of new emerging contaminants (PPCPs and antibiotic resistance genes) combined with traditional heavy metal pollution, indicating that attention should be given to the potential interactive relationships and adverse effects of these materials on the regional ecosystem in the Chao Lake watershed.