Synge Street is located in what once was the Jewish quarter of Dublin a part of the city steeped in history. It is claimed by some historians that the street was named after the Church of Ireland Bishop Edward Synge of Elphin who owned property in the area at the time of his death in 1762. The Bishop was a great-great-great granduncle of John Millington Synge, the famous Playboy of the Western World who wrote The Playboy of the Western World.

The famous Synge Street School, founded in 1864 by the Christian Brothers, has been based in the area ever since it was established.
The main school in the area is Synge Street CBS. The Catholic Church is Harrington Street (St. Kevin's), named after the nearby St. Kevin's medieval church. It was built next to the Christian Brothers monastery in 1871. On the other side of Synge Street is St. Kevin's Hall, which used to be the meeting place for the Catholic Boy Scouts and Girl Guides.

There used to be a Jewish school in Bloomfield Avenue (now Bloomfield House) and synagogues in Walworth Road (established 1917, now the Jewish Museum) and in Adelaide Road but these are all closed now (new facilities have been set up elsewhere). On the Adelaide Road a Presbyterian Church (still functioning) was built in 1841 for a congregation of 800, and in 1863 a smaller chapel for the Irvingites, which later became St. Finian's Lutheran church (also still functioning).

The many Muslims now living in the area attend the Dublin Mosque (formerly the Donore Presbyterian Church, built 1884) further along the South Circular Road, and there is also a centre in Harrington Street. The local Church of Ireland church, St. Kevin's (whose construction, in 1883, was financed by a bequest from a Miss Jane Shannon, of Rathgar, architect, Thomas Drew), was closed in the 1970s and tastefully converted to apartments, while the adjacent church buildings became a community centre. The little church at the top of Victoria Street formerly belonged to the Methodist Congregation, called Kingsland Methodist Church, and after closing in the 1950s was used as a women's Employment Exchange. The Methodists also ran the Female Orphanage School in Harrington Street, which was founded in 1804 and closed in the mid-20th century.

Portobello College was a private institution established in 1989 and located mainly in Portobello House. It was firstly taken over by the Institute of Education (under owner Raymond Kearns) and then in 2009 by the Dublin Business School (owned by Kaplan, Inc, a subsidiary of The Washington Post Company). The students were relocated to the DBS facility in George's St. In 2011, one of India's largest educational institutions, the Rayat Bahra Group, moved into nearby Harbour House, once a part of Portobello College, and set up the Lamrin Business School.

In 2009, a new national and cultural centre was opened in the Christian Brothers monastery on Synge St. called The Lantern, which is aiming to be a place of hospitality to promote intercultural and interfaith dialogue. The name "lantern" was chosen to celebrate the life of Nano Nagle who searched the back lanes of Cork each evening with her lantern seeking those who lacked food and shelter. She inspired Edmund Ignatius Rice to found the Congregation of Christian Brothers and the Presentation Brothers with her work for the poor and disadvantaged.

In May 2011, The new Minister for Justice, Equality and Defence, Alan Shatter opened a Cathal Brugha Barracks Visitors centre to the public commemorating those that fought for the Irish War of Independence.