A Simple tailor-made aldoxime-functionalized water-Soluble polymeric probe (P-Oxime) for the consecutive Colorimetric sensing of multiple analytes, including Hg2+, Ag+, ClO-, and cysteine, was designed and synthesized. A reaction between the aldehyde groups of the side chain in the polymer (P-CHO) and hydroxylamine in ethanol led to the target polymer, P-Oxime. This water-soluble polymeric probe exhibited excellent sensitivity and selectivity toward Hg2+ ions under pH = 5 in water due to the formation of; strong electron-withdrawing nitrile groups (P-CN) via Hg2+-promoted dehydration reaction. The high selectivity and sensitivity of P-Oxime toward ClO- over other reactive o4gen species at pH = 9.5 in water were also observed. After the addition of ClO-, the color of the F-Oxime solution turned from pale yellow to red due to the formation of an aldehyde group: By taking advantage of the formation of functional groups during the Hg2+ and ClO- sensing process, the consecutive sensing/binding studies toward the different analytes were further investigated. The in situ generated P-CN species after Hg2+ detection responded selectively to Ag+ ions with an 18 nm blue-shift in which the nitrile groups of P-CN interacted with the Ag+ ions to form a coordination complex. Similarly, only cysteine and homocysteine among various amino acids showed a remarkable blue-shift upon in situ addition into the obtained P-CHO solutions after ClO- detection via the formation of a thiazolidine ring: