Catholic Seamus Gilmore, 18, was working at a petrol station in north Belfast in February 1973 when he was gunned down.
More than four decades later, detectives have arrested a 59-year-old man from Falkirk and a 61-year-old man from London.
The pair were taken into custody yesterday and are being interviewed in Glasgow and London.
Mr Gilmore was working at a garage in Belfast’s Ballysillan Road when he was shot by loyalists believed to be from the Ulster Volunteer Force (UVF).
Two men got out of a hijacked car driven by another man and fired a number of rounds. Mr Gilmore died in hospital the following day. No-one has ever been convicted of the murder.
Police Service of Northern Ireland (PSNI) serious crime branch detectives travelled to the Falkirk area, where they arrested one suspect with assistance from Police Scotland officers.
At the same time, detectives also travelled to London, where another man was arrested with assistance from the Metropolitan Police.
PSNI Detective Inspector Chris Wilson said: “Following a review process, a number of new lines of inquiry have been identified. I have spoken to the Gilmore family to keep them updated on developments.”
Mr Gilmore was from Rosscoole Park, not far from where he was shot. He was working at the Mount Pleasant filling station in a loyalist area which saw some of the worst violence of the Troubles.
Members of his family released a statement following the development: “We appreciate the efforts of the PSNI which have culminated in these arrests.
“We have forgiven those who took Seamus’s life and we pray for them.
“Our priority now is our 82-year-old mother and we will make no further comment on this matter.”
Det Insp Wilson added that police are still appealing for information about the crime.
He said: “Even though Seamus’s murder took place more than 40 years ago, I would appeal to anyone who has any information about the shooting or who was involved to get in touch with us.
“We are keen to speak with anyone who may have any information which can assist us and we would urge members of the public to contact detectives at Newtownards police station.
“Alternatively, anyone wishing to pass information anonymously can contact the independent charity Crimestoppers on 0800 555 111.”
The PSNI, working with a historical inquiries team, have arrested a number of men in relation to unsolved murders and crimes in Northern Ireland.
Last week, three suspects were arrested in Co Antrim and questioned regarding the shooting of a police officer in 2007.
He was seriously injured after being shot in the shoulder after he left work at Dungannon station on 12 November.
The suspects, aged 36, 37 and 41, were later released pending a report to the Public Prosecution Service.
Northern Ireland’s chief constable recently called violent loyalist protests against a republican dissident rally in Belfast on 9 August “mindless anarchy and sheer thuggery”.
Fifty-six police officers were injured and parts of central Belfast were vandalised as thousands of loyalists sought to prevent a hardline republican alliance, the Anti Internment League, from passing down the city’s main thoroughfare.