The solubility data of poorly soluble anti-inflammatory drug flufenamic acid (FFA) are scarce in literature. Therefore, in the current study, the solubility of FFA in eleven different neat solvents including “water, methanol, ethanol, isopropanol (IPA), ethylene glycol (EG), propylene glycol (PG), 1-butanol, 2-butanol, dimethyl sulfoxide (DMSO), polyethylene glycol-400 (PEG-400) and Transcutol®” was measured and correlated at temperatures “T=298.2K to 318.2K” and pressure “p=0.1MPa”. The solubilities of FFA in mole fraction were measured using a static equilibrium method and correlated with “van't Hoff and Apelblat equations”. The mole fraction solubilities of FFA were obtained maximum in DMSO (2.86×10−1), followed by Transcutol (2.78×10−1), 2-butanol (1.79×10−1), 1-butanol (1.77×10−1), IPA (1.44×10−1), ethanol (1.12×10−1), methanol (6.29×10−2), PEG-400 (6.16×10−2), EG (1.20×10−2), PG (1.81×10−2) and water (1.60×10−6) at “T=318.2K” and similar trends were also recorded at each temperature studied. Activity coefficients were also calculated in order to evaluate the molecular interactions between solute and solvent molecules and results showed higher solute-solvent molecular interactions in FFA-DMSO, FFA-Transcutol, FFA-2-butanol, FFA-1-butanol, FFA-IPA and FFA-ethanol in comparison with other solute-solvent combinations. “Apparent thermodynamic analysis” showed an “endothermic and entropy-driven dissolution” of FFA in all neat solvents studied. Display omitted •Solubility of flufenamic acid (FFA) in different neat solvents was determined.•The mole fraction solubilities of FFA were obtained maximum in DMSO.•Solubilities of FFA were correlated well with calculated ones.•The dissolution of FFA was obtained as endothermic and entropy-driven.