The attack happened at about 5:30 am (0430 GMT) in the Molai district of the city, which has been repeatedly targeted in the past by Boko Haram insurgents.
Borno State Emergency Management Agency spokesman Abdullahi Omar told AFP, "There was an explosion in the mosque in Molai on the outskirts of the city."
"We're waiting for our response team to be back and then give us the details before we can issue any statement."
But a source at the agency added, "This morning just before prayers two women disguised as men came by the mosque. One of them went in and joined the first row of the congregation and when the worshippers stood up for the prayers she detonated her explosives, killing several worshippers."
"While the others were trying to flee, the second woman who stood outside the mosque rushed in and set off her explosives in their midst. Rescue is still ongoing but so far 22 people have been confirmed dead and 35 others injured."
The source, who asked for anonymity as he was not authorized to talk to the media, said survivors of the attack and evidence from the rescue operation identified the bombers as women.
The attack bore all the hallmarks of Boko Haram terrorists, who have regularly hit "soft" civilian targets such as mosques, markets and bus stations, including with female suicide bombers.
Maiduguri, where the group was formed in 2002, has been relatively calm in recent months as a result of heavy security and a sustained counter-offensive against the militants last year.
Nigeria has said the rebels, whose insurgency has left at least 17,000 dead since 2009, have been "technically" defeated, despite continued attacks in Borno state and neighbouring Cameroon.
On January 31, at least 85 people were killed when insurgents attacked the village of Dalori, some 12 kilometres (seven miles) from Maiduguri.
The city itself was last attacked on November 22 last year when a female suicide bomber blew herself up among a crowd of women and children seeking sanctuary from the rural town of Dikwa.
Eight people were killed.
A twin suicide attack on a mosque in Molai on October 15 last year killed 30 and injured 32. The previous June 27, a suicide bomber left five dead in a blast outside a leprosy centre in the area.