Zinc oxide (ZnO) and its ternary alloy magnesium zinc oxide (Mg _x Zn_1−x O) are piezoelectric materials that can be used for high-quality-factor bulk acoustic wave (BAW) resonators operating at GHz frequencies. Thin-film bulk acoustic resonators (TFBARs) are attractive for applications in advanced communication and in various sensors as they offer the capability of monolithic integration of BAW resonators with radio-frequency integrated circuits (RF ICs). In this paper we report Mg _x Zn_1−x O-based TFBAR biosensors. The devices are built on Si substrates with an acoustic mirror consisting of alternating quarter-wavelength silicon dioxide (SiO₂) and tungsten (W) layers to isolate the TFBAR from the Si substrate. High-quality ZnO and Mg _x Zn_1−x O thin films are achieved through a radio-frequency (RF) sputtering technique. Tuning of the device operating frequency is realized by varying the Mg composition in the piezoelectric Mg _x Zn_1−x O layer. Simulation results based on a transmission-line model of the TFBAR show close agreement with the experimental results. ZnO nanostructures are grown on the TFBAR’s top surface using metal- organic chemical vapor deposition (MOCVD) to form the nano-TFBAR sensor, which offers giant sensing area, faster response, and higher sensitivity over the planar sensor configuration. Mass sensitivity higher than 10³ Hz cm²/ng is achieved. In order to study the feasibility of the nano-TFBAR for biosensing, the nanostructured ZnO surfaces were functionalized to selectively immobilize␣DNA, as verified by hybridization with its fluorescence-tagged DNA complement.