They believe the two suspects were involved, along with Abdelbaset al-Megrahi – the only person to have been convicted of the 1988 atrocity.
A total of 270 people died in the bombing.
Megrahi was released in 2009 on compassionate grounds after being diagnosed with prostate cancer. He died in 2012, protesting his innocence.
Scotland’s Lord Advocate Frank Mulholland QC recently met the US Attorney General, Loretta Lynch, in Washington to review progress made in the ongoing investigation.
They have now requested permission from the Libyan authorities for Scottish police and the FBI to interview the two named suspects in Tripoli.
A Crown Office spokesman said: “The Lord Advocate and the US Attorney General have recently agreed that there is a proper basis in law in Scotland and the United States to entitle Scottish and US investigators to treat two Libyans as suspects in the continuing investigation into the bombing of flight Pan Am 103 over Lockerbie.
“The Lord Advocate has today, therefore, issued an International Letter of Request to the Libyan attorney general in Tripoli which identifies the two Libyans as suspects in the bombing of flight Pan Am 103.
“The Lord Advocate and the US Attorney General are seeking the assistance of the Libyan judicial authorities for Scottish police officers and the FBI to interview the two named suspects in Tripoli.
“The two individuals are suspected of involvement, along with Abdelbaset Ali Mohmed al-Megrahi, in the bombing of flight Pan Am 103 in December 1988 and the murder of 270 people.”
Megrahi’s part in the bombing has been called into question in a series of books and documentaries.
And a petition seeking “Justice For Megrahi”, backed by politicians and family members of some victims, was raised at the Scottish Parliament in 2012.
In December last year, Mr Mulholland said no Crown Office investigator or prosecutor had ever raised concerns about the evidence used to convict Megrahi.
He also pledged to continue tracking down Megrahi’s accomplices.
A man who was originally accused of the bombing alongside Megrahi, Lamin Khalifah Fhimah, was found not guilty.
The trial, at Camp Zeist in the Netherlands, which began in May 2000 and lasted 36 weeks, heard that Fhimah was in Sweden at the time of the sabotage and could not have been a participant.
After the judges delivered their unanimous verdict, he was freed and returned to his home at Souk al-Juma in Libya on 1 February 2001.
The ongoing investigation into the bombing remains a joint one between US and Scottish prosecutors, Police Scotland and the FBI.
The Pan Am flight was on its way from London to New York when it exploded above Lockerbie, in southern Scotland, on the evening of 21 December 1988, killing everyone on board and 11 people on the ground.
Megrahi was found guilty of mass murder and was jailed for life with a minimum term of 27 years behind bars. He lost his first appeal in 2002.
The following year, he applied to the Scottish Criminal Cases Review Commission (SCCRC) for a review of his conviction.
A £1.1m investigation by the body led to a finding in June 2007 of six grounds where it believed a miscarriage of justice may have occurred.
This decision opened the door to Megrahi’s second appeal against his conviction. Although a number of hearings had already been held before senior appeal judges, he dropped his appeal two days before being released from prison in August 2009.
Earlier this year, Scottish judges ruled that relatives of the victims of the Lockerbie bombing should not be allowed to pursue an appeal on Megrahi’s behalf.
The group of British relatives had argued they had a “legitimate interest” in trying to get his case back before a court for a full appeal.
The SCCRC had asked the Appeal Court in Edinburgh for guidance on whether members of the victims’ families could take such a legal move forward.
But judges ruled in July that the law was “not designed to give relatives of victims a right to proceed in an appeal for their own or the public interest”.