The suicide blasts took place in Molai district in the city of Maiduguri at about 5:30am (local time).
The attack bore all the hallmarks of Boko Haram Islamists, who have regularly hit “soft” civilian targets such as mosques, markets and bus stations, including with female suicide bombers.
Borno State Emergency Management Agency spokesman Abdullahi Omar and army spokesman Sani Usman confirmed the blast.
“Sadly, 22 people were killed and 18 others sustained various degrees of injuries,” Mr Usman said in a statement.
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.”
The source, who asked for anonymity as he was not authorised to talk to the media, said survivors of the attack and evidence from the rescue operation identified the bombers as women.
Maiduguri, where Boko Haram 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.