A pick-up truck loaded with explosives was detonated as it drove towards a security office where civilians were gathering to organise returning to their homes.
“A small civilian pick-up truck reached the gathering and went off at the security checkpoint,” said Mohammed al-Tawil, commander of a Turkish-backed rebel faction fighting in the area.
Footage showed bodies and remains strewn across the ground, with shrapnel-ridden cars and motorbikes tossed on their side and set on fire by the blast.
Most of the victims were believed to be men, women and children seeking permits to return to their homes in al-Bab and the surrounding area, which is gradually being freed from more than three years of Isis control.
The security office in Susiyan is in charge of issuing documents and providing an escort for civilians wishing to return to al-Bab.
Mr Tawil said at least two groups of about 150 civilians had already left for the city earlier on Friday, accompanied by a minesweeping unit operated by the Syrian opposition fighters.
“These people have suffered a lot...it was very difficult, and they have been waiting for this moment [to return home],” he added.
More than 40 victims injured by the blast were transferred over the Turkish border to the city of Kilis to be treated in a state hospital.
A second car bombing in Susiyan was reported by activists hours later, leaving at least eight people dead.
Isis regularly uses car bombs in battle in Syria and Iraq, including one driven into government forces by a British militant in Mosul, but has used them less frequently against civilian targets.
The attacks struck about five miles from al-Bab, as opposition fighters continue battles to push jihadis back in northern Syria.
They are being reinforced by Turkish air strikes, weapons, tanks and troops sent over the border last year amid increasing concern in Ankara over territory gained by Kurdish group.
Binali Yildirim, the Prime Minister, said at least six Turkey-backed soldiers were killed in the Susiyan bombing before another explosion near al-Bab killed two Turkish soldiers on Friday.
The improvised explosive device went off as they patrolled on roads near Tadef, a town still controlled by Isis south of the city.
The deaths raise the known death toll of Turkish soldiers in northern Syria to 70 since they entered in August.
The so-called Islamic State withdrew from al-Bab following a two-month offensive on Thursday but remains in control of the surrounding area, with multiple front lines controlled by opposition rebels, the Syrian government and Kurdish forces.
At least seven opposition fighters have been killed in al-Bab by landmines left behind by Isis – a trademark of its bloody retreats in Syria and Iraq.
In pictures: Civilians freed from Isis in Manbij
In pictures: Civilians freed from Isis in Manbij
Women and children celebrating after being freed from Isis in Manbij, Syria, on 12 August
A man cuts the beard of a civilian who was freed from Isis by the SDF in Manbij on 12 August
Women carry newborn babies while running after being freed from Isis in Manbij, Syria, on 12 August
A woman freed from Isis hugs an SDF fighter in Manbij on 12 August
A woman adding her veil to a pile of niqabs burning in Manbij, Syria, after being freed from Isis on 12 August
Children celebrating on top of a lorry after being freed from Isis in Manbij, Syria, on 12 August
A man and child freed from Isis by the SDF in Manbij on 12 August
A woman carrying her children walks towards SDF fighters after being freed from Isis in Manbij, Syria, on 12 August
A woman and child freed from Isis in Manbij, Syria, on 12 August
An SDF fighter kisses a crying man who was freed from Isis in Manbij, Syria, on 12 August
Hundreds of civilians freed from Isis in Manbij, Syria, on 12 August
Before the outbreak of the Syrian civil war, al-Bab had a population of approximately 60,000 people but many were displaced into neighbouring areas by fighting.
Footage from the city centre showed it completely deserted and badly damaged by intense battles, with at least one street levelled to the ground and others made impassable by trenches and earth mounds.
The offensive continued on Friday amid air strikes by the US-led coalition in the region, hitting Isis targets in al-Bab, Raqqa, Deir Ezzor, al-Shaddadi and near Palmyra.
Meanwhile, Iraqi forces made crucial gains in Isis’s Iraqi capital of Mosul, progressing through western districts after retaking the city’s airport.
Haider al-Abadi, Iraq’s Prime Minister, ordered his air force to carry out strikes over the border in Syria amid fears jihadis would flee the advance and consolidate their power elsewhere.
He described the operation as a “great success”, with Syrian foreign ministry sources saying the raid was carried out in coordination with Bashar al-Assad’s government.
A second day of peace talks were underway in Geneva, but hopes of a political solution are wearing thin after almost six years of brutal civil war.
Additional reporting by agencies