An evanescent field sensor utilizing layered polymeric-inorganic composite waveguide configuration was developed in this work. The composite waveguide structure consists of a UV-imprint patterned polymer inverted rib waveguide with a Ta2O5 thin film sputter-deposited on top of the low refractive index polymer layers. The results suggest that the polymer based sensor can achieve a detection limit of 3 × 10−7 RIU for refractive index sensing and corresponding limit of about 100 fg/mm2 for molecular adsorption detection. Besides enhancing the sensitivity significantly, the inorganic coating on the polymer layer was found to block water absorption effectively into the waveguide resulting in a stabilized sensor operation. The ability to use the developed sensor in specific molecular detection was confirmed by investigating antibody – antigen binding reactions. The results of this work demonstrate that high performance sensing capability can be obtained with the developed composite waveguide sensor.