El-Sayed was born in Zifta, Egypt and spent his early life in Cairo. He earned his B.Sc. in chemistry from Ain Shams University Faculty of Science, Cairo in 1953. El-Sayed earned his doctoral degree in chemistry from Florida State University working with Michael Kasha, the last student of the legendary G. N. Lewis. While attending graduate school he met and married Janice Jones, his wife of 48 years. He spent time as a post-doctoral researcher at Harvard University, Yale University and the California Institute of Technology before joining the faculty of the University of California at Los Angeles in 1961. In 1994, he retired from UCLA and accepted the position of Julius Brown Chair and Regents Professor of Chemistry and Biochemistry at the Georgia Institute of Technology. He led the [http://www.ldl.gatech.edu/ Laser Dynamics Lab] there until his full retirement in 2020.
El-Sayed is a former editor-in-chief of the Journal of Physical Chemistry (1980–2004).