ABSTRACT The presence of sulfonamide antibiotic residues, such as sulfadiazine (SDZ), in aquatic ecosystems presents significant ecological risks, including the emergence of antibiotic resistance. Therefore, the development of precise and sensitive detection methods is of paramount importance. This study focuses on the design of a highly sensitive sensor for detecting SDZ by exploring the effects of quantum dot (QD) emission wavelength, particle size, and surface characteristics on sensor performance. Green, yellow, and red‐emitting cadmium telluride (CdTe) QDs were synthesized through systematic adjustments in the molar ratio of Cd 2+ to Te, reflux time, and solution pH. These QDs were subsequently incorporated into silica nanoparticles (NH 2 ‐SiO 2 ) via molecular imprinting technology to fabricate a multicolor fluorescent imprinted sensor. The results indicated that the sensor incorporating green‐emitting QDs (MIPs@g‐QDs@SiO 2 ) exhibited the best performance, with a detection limit of 10.53 nM, a fluorescence quenching constant of , and a linear detection range of 10–60 μmol·L −1 . In comparison, the yellow and red‐emitting QD sensors displayed higher detection limits of 30.58 and 68.52 nM, with quenching constants of and , respectively. The sensitivity of the green‐emitting QD sensor is attributed to its smaller particle size, which results in a larger specific surface area and enhanced surface effects, thereby increasing the fluorescence intensity range. Moreover, fluorescence quenching and selective adsorption experiments demonstrated that MIPs@g‐QDs@SiO 2 exhibited excellent selective adsorption properties for SDZ, contributing to its enhanced fluorescent response.