He has participated for many years at Goddard Space Flight Center in study of planetary atmospheres and development of space qualified instrumentation.

Paul Mahaffy served until his retirement in December 2021 as the Principal Investigator (PI) on the Sample Analysis at Mars Instrument Suite on the Curiosity Rover currently operating on the surface of Mars as well as the PI on the Neutral Gas and Ion Mass Spectrometer on the MAVEN Mars orbiter mission, and the PI on the Neutral Mass Spectrometer on the LADEE mission that recently finished a very successful mission in lunar orbit exploring the tenuous lunar exosphere. One of his past career highlights was studying the atmosphere of Jupiter using data from a mass spectrometer on the Galileo Probe as it parachuted down into that atmosphere and sent its data back to Earth.