The station was on the site of a former linen mill, beside where Durham Street crossed the Blackstaff River at the Saltwater (now Boyne) Bridge.

The Ulster Railway opened the first station on 12 August 1839 (1839-08-12). A new terminal building, probably designed by Ulster Railway engineer John Godwin, was completed in 1848. Godwin later founded the School of Civil Engineering at Queen's College.

The station, built directly on Victoria Street, was Belfast's first railway terminus, and as such was called just "Belfast" until 1852. By this time, two other railway companies had opened termini in Belfast, so the Ulster Railway renamed its terminus "Belfast Victoria Street" for clarity. In 1855 the Dublin and Belfast Junction Railway was completed, making Victoria Street the terminus for one of the most important main lines in Ireland. The Ulster Railway changed the station name again to "Great Victoria Street" in 1856, in line with a change of the street name.

In 1876 the Ulster Railway became part of the Great Northern Railway (GNR), making Great Victoria Street the terminus for a network that extended south to Dublin and west to Derry and Bundoran.

Express passenger traffic to and from Dublin Connolly station was always Great Victoria Street's most prestigious traffic. The GNR upgraded its expresses over the decades and in 1947 introduced the Enterprise non-stop service between the two capitals. As Belfast suburbs grew, commuter traffic also grew in volume.

In 1958, the Ulster Transport Authority took over Northern Ireland's bus and rail services. Three years later Great Victoria Street station was modernised, and a bus centre incorporated into the facility. Then in 1968, a large section of the 1848 terminal building was demolished to make way for the development of the Europa Hotel, which opened in 1971.

During the conflict known as The Troubles, the station was attacked several times. On 22 March 1972, 70 people were injured, a train was destroyed and the station significantly damaged by a Car bomb. Another bomb explosion, on 21 July, destroyed four buses but caused no casualties. This was one of 20 bombs that exploded that day, planted by the Provisional Irish Republican Army in an event that became known as Bloody Friday

In April 1976 Northern Ireland Railways closed both Great Victoria Street and the Belfast Queen's Quay terminus of the Bangor line and replaced them both with a new Belfast Central Station, now renamed Lanyon Place. The remainder of Great Victoria Street station was demolished. After a feasibility study was commissioned in 1986 it was agreed that a new development on the site, incorporating the reintroduction of the Great Northern Railway, was viable. The Great Northern Tower had already been built on the site of the old station terminus in 1992, and so the second Great Victoria Street Station was built behind the tower block, yards from the site of its predecessor. The new station was opened on 30 September 1995. The station closed on Friday 10 May 2024 to make way for the new Belfast Grand Central station. The last train to depart was the 23:32 service to Bangor.

The final station had two island platforms providing a total of four platform faces. Platforms 2 and 3 ran the full length of the site and opened onto the station's main concourse. Platforms 1 and 4 were half the length and were accessible by walking down the other platforms.

Great Victoria Street was the hub of Northern Ireland's suburban rail services, with Bangor line, Derry~Londonderry line, Newry line and Larne Line trains all terminating there.

On Mondays to Saturdays, there were half-hourly services to Bangor or Portadown on the Bangor and Portadown Lines, with some Portadown-bound trains continuing on to Newry.

There was also a half-hourly service on the Larne Line, with the terminus alternating between Whitehead and Larne Harbour being the terminus every half hour.

Derry~Londonderry Line trains operated hourly from Great Victoria Street to Derry~Londonderry with connecting shuttle service from Coleraine to Portrush via the Coleraine-Portrush railway line.

On Sundays, the Bangor, Larne, and Portadown Line services all reduced to hourly operation. Derry~Londonderry Line services reduced to two-hourly operation, with only seven trains running each way. Derry~Londonderry Line trains were still hourly but alternated between Derry Waterside and Portrush, except for the final train of the evening, which terminated at Coleraine.

Preceding station		Northern Ireland Railways		Following station
Terminus		Northern Ireland Railways Belfast-Derry		City Hospital
		Northern Ireland Railways Belfast-Larne
		Northern Ireland Railways Belfast-Bangor
Adelaide		Northern Ireland Railways Belfast-Newry		City Hospital
	Proposed
Terminus		Enterprise Belfast-Dublin		Portadown
	Historical railways
Terminus		Great Northern Railway (Ireland) Enterprise Express		Amiens Street Line and station open

Railway access from Great Victoria Street at Sydenham linked into George Best Belfast City Airport on the line to Bangor.

NI Railways constructed a new traincare facility next to Adelaide station for its diesel multiple units. The opportunity was also taken to improve the infrastructure at Great Victoria Street; the plan to begin with was to reduce the curves by realigning the track, and moving the buffer stops and the route from the platforms to the concourse to the other side of Durham Street. Additionally there were plans to add a fifth platform to the station, which would have culminated in Enterprise services transferring from Lanyon Place to Great Victoria Street. However, under Translink's subsequent plan to build a new integrated transport hub, the proposal has expanded to the potential construction of a brand new 6–8 platform station on the site of the old Grosvenor Road freight depot, close to the existing station, because the existing site is too constrained for any further expansion. It was announced that the station would close permanently on 10 May 2024, though the line from Belfast to Lisburn would remain open using the third side of the triangular track layout to bypass the GVS/GC site, as services used to do during the station's first closure from 1976-1995.

Great Victoria Street station closed permanently on 10 May 2024.

The Port of Belfast has a Stena Line ferry connecting to Cairnryan for the bus link to Stranraer and onward trains along the Glasgow South Western Line to Glasgow Central.

The Larne line connects with Larne Harbour with P&O Ferries sailing to Cairnryan for the bus link to Stranraer and onward trains along the Glasgow South Western Line to Glasgow Central, as well as alternative sailings by P&O Ferries to Troon also on the Glasgow South Western Line to Glasgow Central.

Great Victoria Street was part of a major public transport interchange, being adjacent to the Europa Buscentre. This was built in 1991 as the ground floor level of a multi-storey car park. The Buscentre is the Belfast terminus for most Ulsterbus "Goldline" services in Northern Ireland. These serve various destinations that are not on the railway network, including Enniskillen, Banbridge, Omagh, Downpatrick, Cavan, Newcastle, Strabane and Armagh. Also, services from the Buscentre serve both Belfast City Airport and Belfast International Airport directly. Ulsterbus runs joint services with Bus Éireann for its direct express service to Dublin and Dublin Airport, with National Express to Dumfries, Carlisle, Manchester, Birmingham, Milton Keynes and London, and with Citylink to Glasgow and Edinburgh.

Europa Buscentre closed permanently on 7 September 2024, with bus services immediately transferring to Belfast Grand Central Station, commencing with a service to Belfast International Airport and Dublin at 5 a.m on 8 September 2024.

• 
  View in 1975 with the Enterprise to Dublin Connolly.
• 
  View of the former GNR railway station when used by Ulsterbus in 1988.
• 
  The closed station being rebuilt in 1995 for NIR services bar the Enterprise.
• 
  View of platforms in 1995.
• 
  Platforms 2 and 3 at Great Victoria Street in August 2007.
• 
  NIR service in 2011 on the Derry~Londonderry railway line.
• 
  The permanent way down the platforms in 2011.

• Media related to Belfast Great Victoria Street railway station at Wikimedia Commons