The novel electro-optic (EO) polymers of fluorinated cross-linkable Y-type polyurethane-imides (PUI) were designed and synthesized by polycondensation of second-order non-linear optical azo-based chromophores, phenyl diisocyanate, and aromatic dianhydride. Molecular structural characterization for the resulting polymers was achieved by proton nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, elemental analysis, and gel permeation chromatography. The resulting polymers exhibited good film-forming properties, high glass transition temperature in the range from 186°C to 198°C and thermal stability up to 300°C, high EO coefficient (γ33 = 43–60 pm/V) at 1550 nm wavelength, good stabilization of electrically induced chromophore dipole alignment and low optical propagation losses in the range of 1.5–1.7 dB/cm at 1550 nm, which are suitable for the EO modulators. Using the synthesized EO PUI as the active core material and of a fluorinated polyimide as cladding material, we have designed and fabricated the high-performance polymer waveguide Mach-Zehnder EO modulators. Obvious modulation was observed by application of ac voltage signal to the EO modulators.