In the human body, edible substances through water-polluting ingredients amplify the antibiotics that lead to harmful influences on health. State-of-the-art methods are inherently required to identify trace impurities in various aqueous mediums. We present amperometry amoxicillin (AMX) sensor fabrication and electrochemical performance using functionalized polyaniline-silver bromide (PANI-AgBr) hybrids. The intramolecular bonds of anilinium and bromide free radicals (–NH-Ag+-O- and –NH-Br°-NH-) give rise to synergistic effects. The flexible polyethylene terephthalate-designed carbon screen-printed electrodes (PET-SPEs) have recognized the AMX concentration. Modified SPEs produce rapidly escalated current amperometry responses. Cyclic voltammetry and linear kinetic analysis authenticate the experimental errors and assess the maximum sensitivity of the AMX antibiotic sensor. The sensor efficiently resulted in the AMX detection under optimized conditions in the ultra-low range (0.193–0.855 nM) and reached the 0.193 nM minimum detection limit. The wide detection range (1–500 ppb) scheme has excellent selectivity, repeatability, and stability, acquiring significant peak potentials to detect the AMX in natural water samples.