This dataset includes per-and polyfluoroalkyl substances (PFAS) and pharmaceuticals monitored at 62 sampling sites in tributaries of the Laurentian Great Lakes. Chemicals were evaluated in a sediment sample (PFAS only) and water concentrations were estimated using polar organic chemical integrative samplers (POCIS). Sediment samples were collected from the 62 sites in June and July 2018, which were analyzed for 23 PFAS compounds using liquid chromatography tandem mass spectrometry (LC/MS/MS). Duplicate sediment samples were collected at 23 sites. Overall, 22 of the 23 sediment PFAS compounds analyzed were detected in samples from at least one site. Pharmaceuticals and PFAS samples were collected instream by deploying two POCIS at each site for approximately 30 days during the period of May through October 2018. POCIS were compromised at two sites, so POCIS data are only included for 60 of the 62 sites. POCIS blanks and replicates were also collected at six sites. Replicate POCIS were deployed within the same stream cross section. Blanks were collected by exposing prepared POCIS to the air during the time it took to deploy and retrieve the sampler. POCIS blank samples were extracted along with field samples at the end of the deployment period. POCIS extracts were analyzed for 107 pharmaceuticals (USGS National Water Quality Laboratory schedule 2440). A separate POCIS extract was analyzed for 34 PFAS using high-performance liquid chromatograph (HPLC) coupled to a triple quadrupole mass spectrometer (MS/MS). Of these compounds, 49 pharmaceuticals and 17 PFAS had POCIS uptake rates, allowing calculations of time-weighted mean concentration over the approximately 30-day deployment. Collectively, there were 69 pharmaceuticals and 21 PFAS detected in environmental POCIS samples.