The synthesis, photophysical properties and E/Z photoisomerization kinetics in solution and in the solid state of a series of three new 3-(-aryl)-1,1,1-trifluoro-3-(2-phenylhydrazono)propan-2-ones (1a–c, Scheme 1) are reported here. Both E and Z isomers were fully characterized by ¹H-, ¹³C- and ¹⁹F-NMR spectroscopy, and single crystal X-ray diffraction analysis was performed for all thermodynamically stable E isomers. The introduction of the trifluoromethyl ketone group as well as the different methyl and trifluoromethyl susbtituents on the hydrazone and the aromatic rings causes significant changes in the photoisomerization dynamics. The N–H⋯F–C(sp³) interaction is believed to have a prominent role in the stabilization of the metastable Z isomer of 1c which has a very slow back thermal isomerization rate compared to 1a and 1b. DFT calculations support the experimental findings and provide the foundation for future design of new photoswitching materials with promising applications in several technological fields.