Metal fuel with high energy and reactivity is an urgent need for the development of solid propellant, explosive and pyrotechnics. Herein, spherical B/Al/PTFE fuel is designed based on synergistic reaction effect between B/F and Al/F and prepared through the confinement-emulsion-templated method. The combustion reaction performance and pressure output performance of B/Al/PTFE microspheres are much better than their physically mixed counterparts. The synergistic reaction effect between B/F and Al/F on the reaction heat, flame propagation, and pressure output were systematically investigated through adjusting the B/Al mass ratio (30/0∼0/30). The DSC results show that the highest heat of combustion of 4904 J/g can be achieved when the B/Al mass ratio is 21/9. Furthermore, the combustion duration, peak pressure, and pressurization rate are monotonically accelerated from 653 ms, 352.15 kPa, and 305.67 MPa/s to 200 ms, 821.25 kPa, and 1831.18 MPa/s, respectively. This work provides a promising method for the design and preparation of highly composited metal fuel for practical application.