Metropolitan Isaiah is a native of New Hampshire, having been born in Portsmouth. He is one of four children born to Dennis and Mary (Kapsimalis) Chronopoulos who had emigrated to the United states from Olympia, Greece. After his primary and high school education, he served with distinction in the United States Marine Corps during the Korean conflict. In the autumn of 1954 he enrolled at Holy Cross Greek Orthodox Seminary in Brookline, Massachusetts. Upon his graduation in 1960, he attended the Ecumenical Patriarchate Seminary of Halki in Istanbul, Turkey for graduate studies.

On December 20, 2002 the Ecumenical Patriarchate elevated the status of the Diocese to a Metropolis, and elected Metropolitan Isaiah is Metropolitan of Denver. The Metropolitan is presently completing his eleventh year in Denver.