Due to their easy, fast, and noninvasive natures, acoustic wave methods have been widely used in the physical property measurements of liquids, such as shear waves for viscosity and ultrasound for density. We investigate the physical interaction between approximately GHz longitudinal acoustic waves and simple Newtonian fluids in micro- and nanoscales, and report a longitudinal-acoustic-wave microsensor for microfluidic bulk-modulus measurement. We also verify that the microsensor is insensitive to viscosity, in contrast to shear-wave sensors commonly used for viscosity measurements. With its small size and nanometer wavelengths, the microsensor in nonreflective regimes can be integrated into microfluidics and can make fast measurements even under harsh conditions, such as in limited (15∼200 µm) channel spaces and sample volumes (approximately µl). The longitudinal-acoustic-waves measuring theory is demonstrated by the Mason model, a finite element analytical model, and experiments on glycerol-water mixture samples. The microsensor is originally designed for microfluidic use, nevertheless, it can be used under diverse conditions in which miniaturization matters, namely, in biomedical, chemistry, industry, environmental, healthcare, energy applications, and so on.