The goal of this work is to provide physical insights into the formation and stability of inclusion complexes (ICs) in aqueous solution between cyclodextrins (CDs) and a common flame retardant, triphenyl phosphate (TPP). Quantum chemistry calculations reveal the possible energetically favorable geometries of TPP in their 1:1 IC form with alpha-, beta-, and gamma-CDs as well as their associated complexation, conformational, and interaction energies. High-resolution mass spectrometry (MS) and tandem MS were used with electrospray ionization to study the soluble ICs formed between TPP and CDs. Successful formation of TPP ICs with both beta- and gamma-CD in solution was detected in the ratio of 1:1 using high-resolution MS in the positive ion Collision-induced dissociation confirmed the formation of TPP ICs with beta- and gamma-CDs by generating two product ions, TPP and beta- or gamma-CD, in both cases. Although quantum chemistry calculations suggest that IC formation with alpha-CD is energetically possible, an IC with alpha-CD is not observed in aqueous solution using MS, which aligns with what we also previously observed in the solid state. Since TPP forms stable ICs with beta- and gamma-CDs both in the solid state and in solution suggests that complexation could be a safer alternative than applying TPP directly to a substrate. In addition, complexation with CDs in solution also opens up new processing methods to create flame-retardant fabrics and foams with TPP.