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In the present investigation, we demonstrated a simple, rapid, and highly sensitive cladding-modified optical fiber urea sensor based on the evanescent wave absorption (EWA) technique. Cladding modification was performed over a 2-cm unclad portion of optical fiber using a polyaniline-zinc oxide (PANI-ZnO) matrix with enzyme-Urease (Urs) cross-linked to it using glutarldehyde as a cross-linking agent. The PANI-ZnO matrix was characterized by X-ray diffraction, scanning electron microscopy, ultraviolet-visible, and Fourier transform-infrared spectroscopy to explore its various properties. The developed sensor shows a linear response to urea concentration in the range 10 nM−1 M in the form of the absorption spectrum at a wavelength of ~250 nm with specific selectivity. Under the proper conditions (storage at temperature 4°C after each measurement), it shows 40-day stability without any decrement in the intensity of the absorption spectrum. Thus, the developed sensor is highly sensitive, stable, and specific, with a lower detection limit of a urea concentration of 10 nM.