A fire broke out at Thomas Farriner's bakery in Pudding Lane a little after midnight on Sunday, 2 September. The family was trapped upstairs, but managed to climb from an upstairs window to the house next door, except for a maidservant who was too frightened to try, and became the first victim. The neighbours tried to help douse the fire; after an hour the parish constables arrived and judged that the adjoining houses had better be demolished to prevent further spread. The householders protested, and the Lord Mayor Sir Thomas Bloodworth, who alone had the authority to override their wishes, was summoned. When Bloodworth arrived, the flames were consuming the adjoining houses and creeping towards the paper warehouses and flammable stores on the riverfront. The more experienced firefighters were clamoring for demolition, but Bloodworth refused, on the argument that most premises were rented and the owners could not be found. Bloodworth is generally thought to have been appointed to the office of Lord Mayor as a yes man, rather than for any of the needful capabilities for the job; he panicked when faced with a sudden emergency. Pressed, he made the often-quoted remark "Pish! A woman could piss it out", and left. After the City had been destroyed, Samuel Pepys, looking back on the events, wrote in his diary on 7 September 1666: "People do all the world over cry out of the simplicity [the stupidity] of my Lord Mayor in generall; and more particularly in this business of the fire, laying it all upon him."
Around 7 a.m. on Sunday morning, Pepys, who was a significant official in the Navy Office, climbed the Tower of London to get an aerial view of the fire, and recorded in his diary that the eastern gale had turned it into a conflagration. It had burned down several churches and, he estimated, 300 houses, and reached the riverfront. The houses on London Bridge were burning. Taking a boat to inspect the destruction around Pudding Lane at close range, Pepys describes a "lamentable" fire, "everybody endeavouring to remove their goods, and flinging into the river or bringing them into lighters that layoff; poor people staying in their houses as long as till the very fire touched them, and then running into boats, or clambering from one pair of stairs by the water-side to another." Pepys continued westward on the river to the court at Whitehall, "where people come about me, and did give them an account dismayed them all, and word was carried in to the King. So I was called for, and did tell the King and Duke of Yorke what I saw, and that unless his Majesty did command houses to be pulled down nothing could stop the fire. They seemed much troubled, and the King commanded me to go to my Lord Mayor from him, and command him to spare no houses, but to pull down before the fire every way." Charles' brother James, Duke of York, offered the use of the Royal Life Guards to help fight the fire.
A mile west of Pudding Lane, by Westminster Stairs, young William Taswell, a schoolboy who had bolted from the early morning service in Westminster Abbey, saw some refugees arrive in for-hire lighter boats, unclothed and covered only with blankets. The services of the lightermen had suddenly become extremely expensive, and only the luckiest refugees secured a place in a boat.
The fire spread quickly in the high wind. By mid-morning on Sunday, people abandoned attempts at extinguishing the fire and fled; their moving human mass and their bundles and carts made the lanes impassable for firefighters and carriages. Pepys took a coach back into the city from Whitehall, but only reached St. Paul's Cathedral before he had to get out and walk. Handcarts with goods and pedestrians were still on the move, away from the fire, heavily weighed down. The parish churches not directly threatened were filling up with furniture and valuables, which would soon have to be moved further afield. Pepys found Mayor Bloodworth trying to coordinate the firefighting efforts and near collapse, "like a fainting woman", crying out plaintively in response to the King's message that he was pulling down houses. "But the fire overtakes us faster than we can do it." Holding on to his civic dignity, he refused James' offer of soldiers and then went home to bed. Charles sailed down from Whitehall in the Royal barge to inspect the scene. He found that houses still were not being pulled down in spite of Bloodworth's assurances to Pepys, and daringly overrode the authority of Bloodworth to order wholesale demolitions west of the fire zone. The delay rendered these measures largely futile, as the fire was already out of control.
By Sunday afternoon, 18 hours after the alarm was raised in Pudding Lane, the fire had become a raging firestorm which created its own weather. A tremendous uprush of hot air above the flames was driven by the chimney effect wherever constrictions such as jettied buildings narrowed the air current and left a vacuum at ground level. The resulting strong inward winds did not tend to put the fire out, as might be thought; instead, they added fresh oxygen to the flames, and the turbulence created by the uprush made the wind veer erratically both north and south of the main, easterly, direction of the gale which was still blowing.
In the early evening, with his wife and some friends, Pepys went again on the river "and to the fire up and down, it still encreasing." They ordered the boatman to go "so near the fire as we could for smoke; and all over the Thames, with one's face in the wind, you were almost burned with a shower of firedrops." When the "firedrops" became unbearable, the party went on to an alehouse on the south bank and stayed there till darkness came and they could see the fire on London Bridge and across the river, "as only one entire arch of fire from this to the other side of the bridge, and in a bow up the hill for an arch of above a mile long: it made me weep to see it."