The scaling phenomenon poses a great challenge for industrial production because of its widespread presence and the complex scaling process. Hence, we report a novel terpolymer (PIA-SAS-AM) scale inhibitor with high efficiency to obstruct the formation of calcium sulfate. Furthermore, the scale inhibition performance and mechanism were further evaluated and systematically investigated. Herein, the various influence factors (monomer ratio, polymerization temperature, initiator content, etc.) on scale inhibition were discussed in detail. By various characterization methods, the terpolymer scale inhibitor was identified, consistent with the expected structure. Based on the static scale inhibition method, the performance of the copolymer on the control of the CSD (calcium sulfate dihydrate) scale was also explored under different external environments (copolymer concentration, retention temperature, calcium concentration, etc.). Especially, the scale inhibition efficiency of CSD reached nearly 100% when the concentration of the copolymer was 16 mg/L. Additionally, the prepared terpolymer scale inhibitor has great aqueous solubility, salt, and heat resistance. This work provides novel insights into inhibiting crystal scaling and offers further guidance on polymer scale inhibitor design.