The parish was established in 1930, founded by Russian emigrants. Initially, services were held in the home of Boris Timchenko, one of the founders of the parish, on Riggs Place, NW.

In 1936, the community acquired a house at 1768 Church Street, NW. The first floor housed a small chapel that accommodated 30-35 people. The basement was used for church meetings, lectures on Russian culture, and tea gatherings. Some parishioners lived on the upper floor. In the 1940s, after World War II, a new wave of emigration increased the number of parishioners, and the house on Church Street became cramped for the community.

In 1951, a site was purchased for the construction of a church at the corner of Massachusetts Avenue and Edmunds Street, with the construction blessed by Metropolitan Leonty (Turkevich) of All America and Canada. By this time, the number of parishioners had exceeded one hundred.

The church was built as a memorial to the victims of World War I and the Russian Revolution, with soil from Russia laid in its foundation. The design of the church was modeled after the 12th-century Cathedral of Dmitriev in Vladimir.

In May 1955, the lower church was consecrated.

On November 25, 1962, the church was consecrated by Metropolitan Leonty (Turkevich) with the co-celebration of Archbishop Irenei (Bekish) of Boston, Archbishop John (Shakhovsky) of San Francisco, and Bishop Cyprian (Borisevich) of Washington.

Services in English began in the 1950s, and from 1965, the Divine Liturgy in English was held once a month. Since 1971, two Sunday liturgies were served: in English and Church Slavonic.

In 1970, the American Metropolia received autocephaly from the Moscow Patriarchate, and the Nicholas Church became the cathedral of the Orthodox Church in America.

In 1988, a bell tower was added to the church, consecrated in honor of Saint Prince Vladimir and the millennium of the Baptism of Rus.

In October 1991, icon painters from Moscow arrived in Washington to paint the cathedral. They developed an iconography program in the Russian-Byzantine style of the 12th century, corresponding to the architectural model of the Nicholas Cathedral. Their work was completed in 1994, in time for the celebration of the 200th anniversary of Orthodoxy in America.