In this work, we revisited the single-step synthesis of CdE (E = S, Se, and Te) quantum dots (QDs). Powdered CdO and elemental chalcogen were directly used for heating-up synthesis. Firstly, the in situ dissolution of the solid precursors and related QD formation channels were preliminarily investigated. In general, QDs were generated from homogeneous reactions between dissolved cadmium and chalcogen precursors in bulk solution. We found that, during single-step synthesis, both the dissolution of CdO and selenium proceeded faster than their ex situ dissolution respectively. To explain this result, we proposed the existence of extra surface reaction channels for QD formation. That is, QDs could also be generated via on-surface reactions between the solid precursors and the dissolved counter precursors (as “ligands”). The happening of these extra surface reactions would increase the overall dissolution rate of CdO and selenium. Further, the circulation of oleic acid which is peculiar to such single-step synthesis should also partly account for the accelerated dissolution of CdO. Finally, by comparing with two-step synthesis using pre-dissolved CdO, we presented that such single-step synthesis was reliable in making uniform CdE QDs with good reproducibility. Our work reaffirmed the great potential of this single-step strategy in cost-effective synthesis of monodisperse QDs. Moreover, the ligand-promoted surface reaction channels would be applicable in solution-phase synthesis of metal chalcogenide nanocrystals from solid precursors.