Libya's former rebels, now the country's de facto rulers, claimed the convoys were a major flight by Gaddafi's most hardcore backers from his final strongholds.
The claims could not immediately be confirmed. Information on the size of the convoys and who was in them was scarce as they made their way across the vast swath of Sahara, over 1,609 km, between any populated areas on the two sides of the border.
But as the first group of a dozen vehicles pulled into Niger's capital Niamey on Tuesday, a customs official confirmed that it included Mansour Dao, Gaddafi's security chief and a key member of his inner circle, as well as around 12 other Gaddafi regime officials.
The official, Harouna Ide, told The Associated Press that other Libyan convoys had passed through Agadez, a town about halfway between Niger's border with Libya and its capital in the far southwest.
Gaddafi himself is not in the convoys, Niger's Foreign Minister Bazoum Mohamed said, according to Al-Arabiya television.
A significant flight by Gaddafi's senior regime figures could bring an important shift as the opposition forces that swept into Tripoli on August 21 and toppled the longtime leader struggle to shut down the last holdouts of his supporters.
Three major cities remain under Gaddafi's sway, Bani Walid, Sirte and Sabha. The anti-Gaddafi leadership has been negotiating with tribal leaders in Bani Walid to try to arrange a peaceful entry of its forces into the city, but talks have made little headway amid deep suspicions between the two sides.
Opposition officials have depicted the populations in Bani Walid and the other towns as divided, with some prepared to surrender, some still backing Gaddafi, and with a hard core of former regime figures forcing the towns to dig in.
Gaddafi spokesman Moussa Ibrahim was defiant in a Tuesday phone call to the Syrian TV station al-Rai, saying the ousted leader was "in excellent health, planning and organising for the defence of Libya." Ibrahim, who the rebels believe was in Bani Walid, said both Gaddafi and his sons remain in Libya.
"We are fighting and resisting for the sake of Libya and all Arabs," he said. "We are still strong and capable of turning the tables on NATO," he said, though the regime effectively collapsed more than a week ago.
But many in the new leadership depicted the move as a significant run for the border by Gaddafi's inner circle.
Guma El-Gamaty, a British-based spokesman for the National Transitional Council(NTC), the de facto government, said the convoys included "the heavyweight political, military and media officials and officers" and described them as " a turning point" that could lead to the handover of Bani Walid and Sirte.
A representative of Sirte in the NTC, Hassan Droua, said he had reports from witnesses inside the city that a convoy of cars belonging to Gaddafi's son Moatassim had left Sirte, heading south toward the Niger border, after they were loaded with cash and gold from the city's Central Bank branch.
Droua said there were negotiations on Tuesday with tribes in Sirte for the handover of the city, located on the Mediterranean coast 400 kilometres southeast of Tripoli.
Fadl-Allah Haroun, a commander in Benghazi where the NTC remains based, also said there were talks with Sirte residents and that he had reports of as many as 250 vehicles in fleeing convoys.
Some members of Gaddafi's family, including his wife, his daughter Aisha and two of his sons, recently sought refuge in Algeria.
In Tripoli, the new leadership's fighters seized Khalid Kaim, Gaddafi's deputy foreign minister, at his home on Monday, another official, Khaled al-Zintani, said.
