For aerospace applications, honeycomb sandwich panels may have small perforations on the cell walls of the honeycomb core to equilibrate the internal core pressure with external gas pressure, which prevent face-sheet/core debonding due to pressure build-up at high temperature. We propose a new form of perforation on the cell walls of honeycomb sandwich panels to reduce the influence of the perforations on the cell walls on the mechanical properties. In this paper, the high temperature mechanical properties of a new vented Ti-6Al-4V honeycomb sandwich panel were investigated. A vented Ti-6AL-4V honeycomb sandwich panel with 35Ti-35Zr-15Cu-15Ni as the filler alloy was manufactured by high-temperature brazing. The element distribution of the brazed joints was examined by means of SEM (scanning electron microscopy) and EDS (energy-dispersive spectroscopy) analyses. Compared to the interaction between the face-sheets and the brazing filler, the diffusion and reaction between the honeycomb core and the brazing filler were stronger. The flatwise compression and flexural mechanical properties of the vented honeycomb sandwich panels were investigated at 20, 160, 300, and 440 °C, respectively. The flatwise compression strength, elastic modulus, and the flexural strength of the vented honeycomb sandwich panels decreased with the increase of temperature. Moreover, the flexural strength of the L-direction sandwich panels was larger than that of the W-direction sandwich panels at the same temperature. More importantly, the vented honeycomb sandwich panels exhibited good compression performance similar to the unvented honeycomb sandwich panels, and the open holes on the cell walls have no negative effect on the compression performance of the honeycomb sandwich panels in these conditions. The damage morphology observed by SEM revealed that the face-sheets and the brazing zone show ductile and brittle fracture behaviors, respectively.