This paper demonstrated a microwave-assisted solvent bonding method that uses organic solvent to seal the thermoplastic substrates with microwave assistance. This direct bonding is a simple and straightforward process that starts with solvent application followed by microwave irradiation without the need for expensive facilities or complex procedures. The organic solvent applied at the bonding interface is used in dissolving and dielectric heating of the thermoplastic surfaces to seal the thermoplastic substrates under microwave assistance. We evaluated acetone and ethanol to seal the polymethyl methacrylate (PMMA) microfluidic device. The bonding performance, such as bonding coverage, geometry stability, and bonding strength (tensile) were observed and compared with the oven-heating and non-heating control experiments under the same force applications. Results showed that the microwave-assisted solvent bonding method presents a high bonding yield (maximum > 99%) and bonding strength (maximum ~2.77 MPa) without microchannel distortion, which can be used for various microfluidic applications.