The structure and dynamic properties of aqueous mixtures of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) have been investigated over the whole range of HFIP mole fraction (xHFIP) by large-angle x-ray scattering (LAXS), small-angle reutron scattering (SANS), F19-, C13-, and O-NMR17 chemical shifts, O-NMR17 relaxation, and mass spectrometry. The LAXS data have shown that structural transition of solvent clusters takes place at xHFIP∼0.1 from the tetrahedral-like hydrogen bonded network of water at xHFIP⩽∼0.1 to the structure of neat HFIP gradually formed with increasing HFIP concentration in the range of xHFIP⩾0.15. The Ornstein–Zernike plots of the SANS data have revealed a mesoscopic structural feature that the concentration fluctuations become largest at xHFIP∼0.06 with a correlation length of ∼9 Å, i.e., maximum in clustering and microhetrogeneities. The F19 and C13 chemical shifts of both CF3 and CH groups of HFIP against xHFIP have shown an inflection point at xHFIP∼0.08, implying that the environment of HFIP molecules changes due to the structural transition of HFIP clusters. The O17 relaxation data of water have shown that the rotational motion of water molecules is retarded rapidly upon addition of HFIP into water up to xHFIP∼0.1, moderately in the range of ∼0.1<xHFIP≲0.3, and almost constant at xHFIP≳0.3, reflecting the structural change in the solvent clusters at xHFIP∼0.1. The mass spectra of cluster fragments generated in vacuum from HFIP-water mixtures have shown that the predominant clusters are A1Wn (n<12, A=HFIP, W=water) and water clusters Wn (n=5–8) at xHFIP=0.09 and 0.20 and only HFIP oligomers in a water-rich region of xHFIP=0.005∼0.01. From all the information obtained in the present study, the models are proposed for the aggregation of HFIP and water molecules in HFIP-water mixtures.