Ibuprofen, a non-steroidal anti-inflammatory pain reliever, is among pharmaceutical residues of environmental concern ubiquitously detected in wastewater effluents and receiving rivers. Thus, ibuprofen removal potentials and associated bacteria in the hyporheic zone sediments of an impacted river were investigated. Microbially mediated ibuprofen degradation was determined in oxic sediment microcosms amended with ibuprofen (5, 40, 200, and 400 µM), or ibuprofen and acetate, relative to an un-amended control. Ibuprofen was removed by the original sediment microbial community as well as in ibuprofen-enrichments obtained by re-feeding of ibuprofen. Here, 1-, 2-, 3-hydroxy- and carboxy-ibuprofen were the primary transformation products. Quantitative real-time PCR analysis revealed a significantly higher 16S rRNA abundance in ibuprofen-amended relative to un-amended incubations. Time-resolved microbial community dynamics evaluated by 16S rRNA gene and 16S rRNA analyses revealed many new ibuprofen responsive taxa of the Acidobacteria, Actinobacteria, Bacteroidetes, Gemmatimonadetes, Latescibacteria, and Proteobacteria. Two ibuprofen-degrading strains belonging to the genera Novosphingobium and Pseudomonas were isolated from the ibuprofen-enriched sediments, consuming 400 and 300 µM ibuprofen within three and eight days, respectively. The collective results indicated that the hyporheic zone sediments sustain an efficient biotic (micro-)pollutant degradation potential, and hitherto unknown microbial diversity associated with such (micro)pollutant removal.