Karplus received the 2013 Nobel Prize in Chemistry, together with Michael Levitt and Arieh Warshel, for "the development of multiscale models for complex chemical systems".

[8][9] He was a child when his family fled from the Nazi-occupation in Austria a few days after the Anschluss in March 1938, spending several months in Zürich, Switzerland and La Baule, France before immigrating to the United States.

[13] He was the nephew, by marriage, of the sociologist, philosopher and musicologist Theodor W. Adorno and grandnephew of the physicist Robert von Lieben.

Continuing with the academic family theme, his nephew, Andrew Karplus, is a biochemistry and biophysics professor at Oregon State University.

[14] After earning an AB degree in Chemistry and Physics from Harvard College in 1951,[15] Karplus pursued graduate studies at the California Institute of Technology.

[8][16] He was a professor at the Louis Pasteur University in 1996 where he established a research group in Strasbourg, France, after two sabbatical visits between 1992 and 1995 in the NMR laboratory of Jean-François Lefèvre.

The Karplus equation describing the correlation between coupling constants and dihedral angles in proton nuclear magnetic resonance spectroscopy is named after him.