Muhammad Asim Khan, a spokesman for Peshawar's Lady Reading Hospital, said the death toll had climbed to 56, the deadliest since a July 2018 blast -- claimed by the local chapter of the Islamic State group -- killed 149 people at an election rally.
He said 50 of the 194 wounded were in "critical condition". Muhammad Ali Saif, a spokesman for the Khyber Pakhtunkhwa provincial government, told AFP the blast was a "suicide attack" and numerous witnesses recounted the moment of detonation.
Ali Asghar saw a man enter the mosque before Friday prayers and open "fire with a pistol", picking out the worshippers "one-by-one". He "then blew himself up", Asghar said.
"I saw a man firing at two policemen before he entered the mosque. Seconds later I heard a big bang," said another witness, Zahid Khan.
The head of Peshawar's bomb disposal unit, Rab Nawaz Khan, told AFP the attacker detonated five to eight kilograms (two to four pounds) of "highly explosive TNT" packed with ball bearings to amplify the damage.
An AFP reporter saw body parts strewn at the blast site, where desperate family members were held back by police.
Police officers shot
Peshawar police chief Muhammad Ijaz Khan told AFP two attackers were involved.
He said two police officers were shot at the entrance of the mosque. "One policeman died on the spot while the other was critically injured," he said.
Muhammad Asim Khan, a spokesman for Peshawar's Lady Reading Hospital, said "we have declared an emergency at the hospitals and more injured are being brought".
A spokesman for Prime Minister Imran Khan's office said he "strongly condemned" the attack.
No group immediately claimed responsibility for the bombing.
Peshawar -- just 50 kilometres from the porous border with Afghanistan -- was a frequent target of militants in the early 2010s but security has greatly improved in recent years.
Sunni majority Pakistan has recently been battling a resurgence of its domestic chapter of the Taliban, Tehreek-e-Taliban Pakistan (TTP).
A one-month truce last year failed to hold and there are fears the TTP -- which has targeted Shia Muslims in the past -- has been emboldened by the success of the Afghan Taliban.
Shiites in the region have also been targeted by the regional iteration of the Islamic State group, Islamic State Khorasan (ISK).
At least 31 people were killed in a suicide blast at a crowded market in Peshawar in 2018.
At least 88 people died and hundreds more were wounded a year earlier when a suicide bomber blew himself up among a crowd of devotees at a revered Sufi shrine in southern Sindh province.