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With the integration strategy of the Yangtze River Delta rising to the height of the national strategy, it is crucial to ascertain pollution, ecological risks, and possible sources of potentially toxic elements (PTEs) in the sediments of the drinking water source channel Taipu River across the core demonstration zone. In this study, distribution, risk assessment, and source of 12 PTEs were investigated in sediment samples from the Taipu River. The concentrations of Mo, Cu, Cd, Ni, and Zn in the sediments of the Taipu River were generally 1.01–5.84 times higher than the background value of the soil from Jiangsu Province. The spatial distribution of PTEs presented differently upstream, middle, and downstream of the river. The values of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>I</mi><mrow><mi>g</mi><mi>e</mi><mi>o</mi></mrow></msub></mrow></semantics></math></inline-formula> and <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>E</mi><mi>F</mi></mrow></semantics></math></inline-formula> showed moderate pollution at individual points, mainly due to Cd, Cu, and Mo. Except for Cd, the average potential ecological risk of other elements was low. Analysis of contamination source indicated that Cr, Ni, Tl, V, As, and Co were from natural sources while Zn, Mo, Cd, Pb, and Sb were associated with industrial activities. Copper was possibly derived from historic aquaculture activities along the Taipu River. Although the concentration of PTEs is generally low, particular attention should be given to Cd, Mo, and Cu as pollution sources. The results provide guidance for controlling PTEs pollution and protecting drinking water sources in the Taipu River.