The blast happened during early morning prayers at the Madina mosque in the Unguwar Shuwa area of Mubi, some 200 kilometres by road from the Adamawa state capital Yola.
It was the biggest attack in Adamawa since December 2016, when two female suicide bombers killed 45 people at a crowded market in the town of Madagali.
Nigeria's President Muhammadu Buhari, who announced nearly two years ago that Boko Haram was "technically defeated", described the blast as "very cruel and dastardly".
Military and civilian militia sources in the northeast said the attack was likely to have been in response to recent increased ground and air operations against Boko Haram.
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Adamawa state police spokesman Othman Abubakar told AFP that "at least 50" people were killed in the Mubi attack, which saw the bomber detonate his explosives among worshippers.
"The bomber was about 17 years old," he added later.
Asked who was responsible, Abubakar said: "We all know the trend. We don't suspect anyone specifically but we know those behind such kind of attacks."
Abubakar Sule, who lives near the mosque, said he was present during the rescue operation and that 40 people died on the spot while several others were taken to hospital with severe and life-threatening injuries.
"The roof was blown off. People near the mosque said the prayer was mid-way when the bomber, who was obviously in the congregation, detonated his explosives.
"This is obviously the work of Boko Haram."
Yan St-Pierre, a counter-terrorism specialist at the Modern Security Consulting Group in Berlin, said the bombing was part of a pattern of increasingly lethal strikes in the last four weeks.
But St-Pierre said despite this "Boko Haram remains an extremely potent and dangerous organisation" which was far from being "on the back foot", as the military and government has claimed.
A civilian militia source embedded with the military told AFP the attack was likely to have been to "shore up morale" after a series of recent losses in the remote region.
On November 19, Boko Haram bases in the Njimiya, Parisa and Gulumba areas near the Sambisa Forest of Borno state were hit by air strikes, leading to "heavy losses", he claimed.
A military source in the Borno state capital, Maiduguri, said there had been more aerial offensives in the Marte, Kukawa, Monguno and Abadam areas of northern Borno.
"They are feeling the heat. They have lost a staggering number of fighters, so they are now fighting back in their usual dastardly way, attacking civilians," he said.
Boko Haram briefly overran Mubi in late 2014 as its fighters rampaged across northeastern Nigeria, seizing towns and villages in its quest to establish a hardline Islamic state.
But it has been peaceful since the military and the civilian militia ousted them from the town, which is a commercial hub and home to the Adamawa State University.
In recent months, Boko Haram activity has been concentrated around Madagali, in the far north of Adamawa near the border with Borno.
There have been repeated raids and suicide bombings, blamed on Boko Haram remnants pushed out of their camps in the Sambisa Forest.
Boko Haram fighters are also said to be hiding in the Mandara mountains, which forms the border of Adamawa and Nigeria with neighbouring Cameroon, where there has also been more attacks.
"It appears that despite open calls for Boko Haram to desist in such acts of mass violence against Muslim civilian interests, that these have not been heeded," he added.