Acoustically triggered microcannons, capable of loading and firing nanobullets (Nbs), are presented as powerful microballistic tools. Hollow conically shaped microcannon structures have been synthesized electrochemically and fully loaded with nanobullets made of silica or fluorescent microspheres, and perfluorocarbon emulsions, embedded in a gel matrix stabilizer. Application of a focused ultrasound pulse leads to the spontaneous vaporization of the perfluorocarbon emulsions within the microcannon and results in the rapid ejection of the nanobullets. Such Nbs “firing” at remarkably high speeds (on the magnitude of meters per second) has been modeled theoretically and demonstrated experimentally. Arrays of microcannons anchored in a template membrane were used to demonstrate the efficient Nbs loading and the high penetration capabilities of the ejected Nbs in a tissue phantom gel. This acoustic-microcannon approach could be translated into advanced microscale ballistic tools, capable of efficient loading and firing of multiple cargoes, and offer improved accessibility to target locations and enhanced tissue penetration properties.