Floodplain soils across Central Elbe River (CER), Germany, vary considerably in potentially toxic element (PTE) content. However, there has never been a comprehensive study that links PTE levels with human health risk for children and adults. Our objective was to determine the contamination of 13 PTEs in 94 soil profiles along CER and assess the associated health risk via diverse indices for adults and children. Of 94 soil profiles, we measured soil properties and total content of arsenic, barium, chromium, copper, nickel, lead, rubidium, tin, strontium, vanadium, zinc, and zirconium using x-ray fluorescence spectrometer (XRF). We calculated the Contamination Factor and the Pollution Load Index (PLI), and assessed the health risk for male and female adults as well as for children. Topsoil median contents of Cr (84 mg kg−1), Cu (42), Ni (33), and Zn (195) exceeded the Precautionary Values for sandy soils according to the German Federal Soil Protection and Contaminated Sites Ordinance, while As, Pb, and V were 32, 73, and 77 mg kg−1, respectively. Median topsoil PLI was 1.73, indicating elevated multi-element contamination, with 90th percentile and maximum values being 3.20 and 4.31, respectively. All PTE concentrations were higher in top- compared to subsoils. Also at the 50th percentile the most enriched elements were Sn and As, followed by Zr and Rb, while in the 90th percentile Sn and As were followed by Zn, Pb and Cu. Median children's hazard index (HI) was higher than unity (HI = 2.27) and the 90th percentile was 5.53, indicating elevated health risk. Adult median HIs were 0.18 for male and 0.21 for female persons. Arsenic was found to be the primary contributor to total risk, accounting of 57.4% of HI in all three-person groupings, with Cr (17.3%) being the second, and V (10.2%) the third. Children's health is at dramatically higher risk than that of adults; also As, Cr, Pb, and V have a predominant role in contamination-related health risks. The presence of V, a less-expected element, among those of major risk contribution, reveals the necessity of monitoring areas at large scale. Our results demonstrate that our study may serve as a model for similar works studying multi-element-contaminated areas in future.