The oldest of six children, Nicholas Dattilo was born in Mahoningtown, Pennsylvania, to Frank and Emma Dattilo. After studying at St. Vincent Seminary in Latrobe and St. Charles Borromeo Seminary in Overbrook, he was ordained to the priesthood on May 31, 1958. He then served as a parochial vicar at in Canonsburg until 1971, also briefly serving at in Turtle Creek. He was pastor of in Swissvale from 1971 to 1981, and of in New Castle from 1981 to 1985. In 1985, he was named Secretary for Clergy and Pastoral Life for the Pittsburgh Diocese, later becoming its vicar general. On November 21, 1989, Dattilo was appointed the eighth Bishop of Harrisburg by Pope John Paul II. He received his episcopal consecration on January 26, 1990 from Archbishop Anthony Bevilacqua, with Bishops William Henry Keeler and Donald William Wuerl serving as co-consecrators, at St. Patrick's Cathedral. As head of the Harrisburg Diocese, he was the leader of the Catholics in South Central Pennsylvania. Shortly after Dattilo's consecration, a three-year Consultations Process was begun to assess the needs and resources of the local Church in preparation for the next century. This resulted in a major reorganization of parishes and missions, because of populations shifts within the fifteen counties of the Diocese. During his tenure, the overall number of parishes was reduced from 120 to 89, resulting in 23 appeals and years of protests. In 1998 Dattilo established the Ecclesial Lay Ministry Program, a three-year formation program to prepare trained lay leaders, and directed that the needs of Catholic schools be studied. Following the closure of Villa Vianney, he approved construction for a new residence for retired priests in 1999. He also finalized plans for a diocesan conference center, with the groundbreaking ceremony being held in October 1999. Dattilo was hospitalized in February 2004 for kidney failure, diabetes and heart and respiratory problems. He later died at in Camp Hill, three days before his 72nd birthday. His funeral Mass was at in Camp Hill, as St. Patrick's Cathedral was undergoing renovations.
On August 1, 2018, Bishop Ronald Gainer, Dattilo's successor as bishop of Harrisburg, announced that the names of every bishop of Harrisburg from 1947 onward -- including Dattilo's -- will be removed from any building or room in the diocese named in their honor, due to their failure to protect victims from abuse.
