Elmessiri was born in Damanhur, Egypt, graduated with a BA in English literature from Alexandria University in 1959. He received a MA in English and comparative literature from Columbia University in 1964 and a PhD in the same field from Rutgers University in 1969. He was professor emeritus of English and comparative literature at Ain Shams University, Egypt since 1988. He was also a University Professor at King Saud University, Saudi Arabia (1983-1988) and at Kuwait University, Kuwait (1988-1989) and a visiting Professor at the International Islamic University Malaysia. He is considered as one of Egypt's most famous thinkers and very well-known among Arab scholars.
Elmessiri's major areas of research included: Jews, Judaism and Zionism; secularism and prejudice; Western culture and contemporaneity; modernism and postmodernism; literary theory and comparative literature. Over the course of his life his outlook moved from western secularism to a modern islamic vision. Elmessiri wrote several articles about his ideas, including "Chosen Community, an Exceptional Burden", "A People Like Any other". He has also written for children.
His eight-volume Encyclopaedia of "Jews, Judaism and Zionism" (" موسوعة اليهود واليهودية والصهيونية: نموذج تفسيري جديد"), written in Arabic with an analytical/methodological form rather than an encyclopedic collection of information, is considered as one of the most authentic works in the field. This work, published in 1999 by Dar El Shorouk, Cairo, was the culmination of around 30 years of research.
On July 2, 2008 he died after a very long battle against cancer at the Palestine Hospital, Cairo.