Understanding the stability and aggregation of nanoparticles in aqueous milieu is critical for assessing their behavior in the natural and engineered environmental systems and establishing their threat to human and ecosystems health. In this study, the colloidal stability and aggregation kinetics of nanocrystal quantum dots (QDs) —CdSe/ZnS QDs—were thoroughly explored under a wide range of aqueous environmental conditions. The z-average hydrodynamic diameters (z-avg. HDs) and zeta potential (ξ potential) of CdSe/ZnS QDs were measured in monovalent electrolyte (NaCl) and divalent electrolyte (CaCl 2 ) solutions in both the absence and presence of natural organic matter (NOM)—Suwannee River natural organic matter, SRNOM to assess the dynamic growth of these nanoaggregate-QD-complexes, and the evaluation of their colloidal stability. Results show that CaCl 2 was more effective to destabilize the QDs compared to NaCl at similar concentrations. An increase in NaCl concentration from 0.01 to 3.5 M increased the z-avg. HD of QD aggregates from 61.4 nm to 107.2 nm. The aggregation rates of QDs increased from 0.007 to 0.042 nm·s −1 with an increase in ionic strength from 0.5 to 3.5 M NaCl solutions, respectively. In the presence of Na + cations, the aggregation of QDs was limited as steric forces generated by the original surface coating of QDs prevailed. In the presence of CaCl 2 , the aggregation of QDs was observed at a low concentration of CaCl 2 (0.0001 M) with a z-avg. HD of 74.2 nm that significantly increased when the CaCl 2 was higher than 0.002 M. Larger sizes of QD aggregates were observed at each level of CaCl 2 concentration in suspensions of 0.002–0.1 M, as the z-avg. HDs of QDs increased from 125.1 to 560.4 nm, respectively. In the case of CaCl 2 , an increase in aggregation rates occurred from 0.035 to 0.865 nm·s −1 with an increase in ionic strength from 0.0001 M to 0.004 M, respectively. With Ca 2+ cations, the aggregation of QDs was enhanced due to the bridging effects from the formation of complexes between Ca 2+ cations in solution and the carboxyl group located on the surface coating of QDs. In the presence of SRNOM, the aggregation of QDs was enhanced in both monovalent and divalent electrolyte solutions. The degree of aggregation formation between QDs through cation-NOM bridges was superior for Ca 2+ cations compared to Na + cations. The presence of SRNOM resulted in a small increase in the size of the QD aggregates for each of NaCl concentrations tested (i.e., 0.01 to 3.5 M, except 0.1 M), and induced a monodispersed and narrower size distribution of QDs suspended in the monovalent electrolyte NaCl concentrations. In the presence of SRNOM, the aggregation rates of QDs increased from 0.01 to 0.024 nm 1 with the increase of NaCl concentrations from 0.01 to 2 M, respectively. The presence of SRNOM in QDs suspended in divalent electrolyte CaCl 2 solutions enhanced the aggregation of QDs, resulting in the increase of z-avg. HDs of QDs by approximately 19.3%, 42.1%, 13.8%, 1.5%, and 24.8%, at CaCl 2 concentrations of 0.002, 0.003, 0.005, 0.01, and 0.1 M, respectively. In the case of CaCl 2 , an increase in aggregation rates occurred from 0.035 to 0.865 nm·s −1 with an increase in ionic strength from 0.0001 to 0.004 M, respectively. Our findings demonstrated the colloidal stability of QDs and cations-NOM-QD nanoparticle complexes under a broad spectrum of conditions encountered in the natural and engineered environment, indicating and the potential risks from these nanoparticles in terms of human and ecosystem health.