The occurrence of Contaminants of Emerging Concern (CECs) in the Pearl River of Guandong province, China, was characterized using a nontarget screening (NTS) strategy combining both data dependent and data independent acquisition techniques. Our analysis identified 620 unique compounds, including pharmaceuticals (137), pesticides (124), industrial materials (68), personal care products (32), veterinary drugs (27), plasticizers or flame retardants (11), etc. Out of these compounds, 40 CECs were found with a detection frequency of over 60 %, including diazepam, a well-known drug to treat anxiety, insomnia, convulsion, etc., which had the highest detection rate at 98 %. Risk quotients (RQs) were calculated for CECs identified with high confidence (Level 1, confirmed with authentic standards), and it was found that 12 CECs had RQs > 1, with notable concern for pretilachlor (detection frequency: 48 %; 0.8–19.0 ng/L), bensulfuron-methyl (86 %, 3.1–56.2 ng/L), imidacloprid (80 %, 5.3–62.8 ng/L) and thiamethoxam (86 %, 9.1–99.9 ng/L), which exhibited RQs exceeding the threshold of concern (RQ > 1) at 46–80 % of sampling sites. Additionally, tentative identification of potential structurally related compounds provided valuable insight into the parent-product relationships in complex samples. This study highlights the importance and urgency of using NTS for CECs in the environment and presents a novel data sharing approach, which facilitates other scientists to assess, investigate further, and perform retrospective analyses.