In 1872 a request was made for a new parish to serve Roman Catholics residing west of Onondaga Creek. The Reverend John J. Kennedy from Saint Mary's Parish in Albany was appointed as the first pastor. Father Kennedy had initially been rejected for priesthood because of near blindness and vowed that, if he recovered his sight, he would dedicate a shrine or church to Saint Lucy. So the new parish became Saint Lucy's. Some 10,000 people attended the laying of the cornerstone on June 21, 1873. Noted architect Archimedes Russell designed the church in the decorative English Gothic style. It was built at the cost of $40,000. The first Mass was celebrated in the church basement on the Feast of All Saints, November 1, 1873. The first Mass in the church proper was celebrated on Christmas Day, 1875. At the time the church comprised 1,000 families and seated about 1,400 people. The parish school, St. Lucy's Academy, opened in 1891.
The parish neighborhood saw dramatic changes in the 1950's, in particular the construction of the nearby public housing. Over the next decades the parish would become more and more involved in meeting the needs of neighborhood residents. One of the first initiatives was a center known as Unity Corner which, under the leadership of Fr. Ray McVey evolved into Unity Acres (a residence of alcoholic and homeless men in Orwell, NY). Later, under Fr. Sizing and Fr. Carey, the current social ministries of the parish were established.
Among more recent developments was the destruction of the church's steeple and bell tower in the Labor Day storm of 1998; the closure of the Academy in 2002; and the merger with the younger St. Andrew the Apostle parish in 2008. Under the leadership of Fr. Joe Kane, the St. Andrew's parish had developed its own vigorous ministries, including work with a sister community in Nicaragua (the Sweet Name of Jesus parish) and the Dorothy Day Dinner (an annual award program for achievement in social justice). Both of these are now ongoing works at St. Lucy's.