A novel difunctional benzoxazine with o-trifluoroacetamide functionality has been synthesized via Mannich condensation. The chemical structure of synthesized monomer has also been confirmed by H-1, C-13, and F-19 nuclear magnetic resonance (NMR) spectroscopy and Fourier transform infrared (FT-IR) spectroscopy. The ring-opening polymerization of the resin and the subsequent conversion of the freshly generated polybenzoxazine into polybenzoxazole are studied by FT-IR and differential scanning calorimetry (DSC). In addition to the advantage of low polymerization temperature as other reported o-amide benzoxazines, the o-trifluoroacetamide benzoxazine also exhibits an unexpected lower benzoxazole formation temperature. Furthermore, the resulting fluorinated polybenzoxazole derived from the benzoxazine monomer possesses the combined excellent properties of facile synthesis, easy processability, low dielectric constant, high thermal stability, and long shelf life, evidencing its potential applications in microelectronic industries, aerospace, and other high-performance areas.