Applying vacuum-based molecular probes of liquid surfaces would aid many environmental, biological, and industrial studies. However the high vapor pressure of water and most organic solvents largely prohibit this use. We report a newly developed versatile and self-contained vacuum interface for high-vapor pressure liquid surfaces, and its application in a time of flight secondary ion mass spectrometer (TOFSIMS) and scanning electron microscope (SEM). The self-contained module requires no wires or tubing connections to the outside of the instrument. It uses a microfluidic channel with a 3 micron diameter window into the flowing fluid beneath it. This window supports the liquid against the vacuum by the liquid’s surface tension, while limiting the high-density vapor region traversed by the probe beams to only a few microns. This aperture size also limits temperature and concentration changes due to evaporation of the solvent. The beam damage caused by the probe beams is largely negligible, as the flowing liquid surface self-renews. We demonstrate the performance of this microfluidic interface for in situ liquid surface TOFSIMS (ISLS-TOFSIMS) and SEM (ISLS-SEM) for chemical analysis of liquid surfaces. This device enables in situ liquid (ISL) studies in a wide range of vacuum analytical methods beyond SEM and TOFSIMS.