Born in Kharkiv, Ukraine, Oleg Prezhdo obtained a Diploma in Theoretical Chemistry in 1991 under Anatoly V. Luzanov from the Kharkiv National University. He worked at the Kharkiv Polytechnic Institute for a year under Stanislav A. Tyurin. Prezhdo moved to the United States in 1993 for his graduate studies and received a Ph.D. from the University of Texas at Austin, working under Peter J. Rossky, in 1997. His doctoral research focused on various quantum-classical approaches in non-adiabatic dynamics in solution.
After a postdoctoral fellowship with John Tully at Yale University, he joined the University of Washington in 1998 as an assistant professor in the department of chemistry. In 2003, he became associate professor and then professor of chemistry (2005–10). In 2010, he moved to the University of Rochester, where he served as a professor of chemistry as well as an adjunct professor of physics. In 2014, he moved to the University of Southern California as a professor of chemistry and physics & astronomy.