Mansfield was born in London and educated at Queen Mary College there, completing his PhD in 1962. After a two-year period at the University of Illinois as a research associate, he took up a position at Nottingham University in 1964; he was professor of physics there from 1979 to 1994.

Mansfield began work in the early 1970s on the use of nuclear magnetic resonance (NMR) to investigate conditions in the human body. The NMR technique was investigated in the 1940s by Bloch and Purcell. It depends on the fact that the nuclei of certain atoms have a net magnetic moment. In an external magnetic field these nuclei can take up allowed orientations with the field direction, each corresponding to a particular quantized energy state. Electromagnetic radiation in the radiofrequency region of the spectrum can be absorbed at a particular resonance frequency corresponding to a transition from one energy state to a higher one. The nuclei, in reverting to the lower state, emit radiation.

Mansfield and his colleagues used this as a nonintrusive method of producing images of the body by detecting the emitted radiation and forming an image by computer-aided tomography (CAT). The x-ray CAT scanner had been developed earlier by Geoffrey Hounsfield. However, light elements such as hydrogen are relatively transparent to x-rays. NMR, on the other hand, is particularly suitable for detecting hydrogen and magnetic resonance imaging (MRI) is especially useful for showing soft tissues. A prototype MRI scanner had been developed by 1980. Initially, it was designed to take cross-sectional images of the brain, but before long whole-body machines were available.