Rare earth elements (REEs) are widely used in various high-tech industries. Developing affinity ligands that can detect and distinguish REEs is at the forefront of analytical chemistry. It is also interesting to understand the limits of natural biomolecules for the recognition of REEs. In this study, Sc3+ was used as a target for the isolation of DNA aptamers, and an aptamer named Sc-1 was obtained. Using a thioflavin T (ThT) fluorescence assay, Sc-1 bound only to REEs, but not other metal ions. Additionally, the binding of Sc-1 to Sc3+ exhibited slow kinetics, and the binding complex resisted dissociation by EDTA. Furthermore, Sc-1 displayed varying binding kinetics with trivalent lanthanide ions, allowing for the discrimination of 17 REEs into three major groups: (1) La3+, Ce3+, Pr3+, Nd3+, Sm3+, Eu3+, and Gd3+; (2) Tb3+, Dy3+, Ho3+, Er3+, Tm3+, Yb3+, Lu3+, and Y3+; and (3) Sc3+. NMR spectroscopy confirmed binding-induced conformational changes in the aptamer. Using the fluorescence strand-displacement method, the true Kd of the aptamer was measured to range from 0.6 to 258.5 nM for the REE ions, and it showed effective detection of Sc3+ in real samples.