"The leader of the Islamic Movement in Nigeria (IMN) Sheikh Ibrahim Zakzaky and his wife have at last just left Nigeria for India alongside some family members and security operatives," his supporters said in a statement.
Two of his lawyers confirmed the cleric's departure from the capital Abuja on an Emirates flight.
Zakzaky has been in custody along with his wife Zeenah Ibrahim since their arrest in December 2015 after violence that saw the army kill some 350 of his followers.
Fears over the couple's health had fuelled a wave of recent protests in Abuja that descended into bloodshed after a brutal crackdown from security forces.
A court last week granted permission for them to receive medical care in India under Nigerian government supervision.
The authorities insist they must return to Nigeria to stand trial once their treatment is completed.
Gunned down
Zakzaky, in his mid-sixties, was arrested in 2015 after the violence in the northern city of Zaria that saw hundreds of his supporters gunned down by security forces and buried in mass graves.
The cleric's lawyers say he has lost his sight in one eye, is on the verge of going blind in the other and still has bullet fragments lodged in his body from the violence. His supporters say he has suffered a series of minor strokes.
A court in 2016 ordered the release of Zakzaky and his wife -- but the authorities refused and filed charges against him including homicide.
Supporters held almost daily protests in Abuja in recent months pushing for his release as fears mounted about his health condition.
At least eight people, including six protesters, a senior police officer and a trainee journalist, were killed during clashes on July 22. The IMN said 20 of its members were shot dead.
The Nigerian government officially outlawed the group late last month in a move that sparked fears of a harsher clampdown.
After the ban, the country's police chief labelled anyone associated with the group an "enemy of the state" and called on the public to help track down its members.
The cleric and his group, which emerged from a student movement in the 1970s, have been at loggerheads with the authorities for years because of calls for an Iranian-style Islamic revolution in Nigeria.
Shias make up a small minority in predominantly Sunni Muslim northern Nigeria. Estimates put their numbers at around four million in a national population of about 190 million.