The rebels tried three assaults on the town. On the first occasion they simply tried to rush the walls. In their second attempt, a small party of 500 men broke into the town at night through dilapidated sections of the walls, with the aim of opening the gates for a storming party of 700 men outside. However, the initial incursion was repulsed in confused fighting and in the morning, the garrison opened the gates to rebels outside, only to take them prisoner once they entered the town. The rebels tried for a final time in March 1642, when a relief of the town was imminent, attacking the walls with scaling ladders, but were again repulsed. Shortly afterwards, English reinforcements arrived from Dublin, under Colonel Moore. They broke the rebel siege and also drove them out of Dundalk and back into Ulster.
Cromwell became known in the English Civil War as an excellent soldier, particularly as a commander of cavalry, but he had little expertise in siege warfare. Rather than go through the lengthy process of blockading a fortified place into surrender, which in any case was not an option because he could not afford to get stuck at Drogheda, he preferred the more risky but quicker option of assault. He positioned his forces on the south side of the river Boyne, in order to concentrate them for the assault and because he was not worried about whether supplies would enter the town from the north. In addition a squadron of Parliamentarian ships blockaded the harbour of the town.
On Monday 10th September Cromwell had a letter delivered to the governor, the English Royalist, Sir Arthur Aston which read: The contemporary laws of war were clear that if surrender was refused and a garrison was taken by an assault, then the lives of its defenders would be forfeit, as Cromwell's letter strongly implies.
Aston refused to surrender so Cromwell opened the bombardment, his cannon battered two large breaches in the town's medieval walls from long range and on the 11 September 1649, Cromwell ordered the assault. Two Parliamentarian attacks were repulsed before Cromwell's men fought their way into the town.
As the Royalists had refused to surrender Cromwell, in his own words, "In the heat of the action, forbade them [his soldiers] to spare any that were in arms in the town". The garrison was massacred as were any Catholic clergy found within the town.
After breaking into the town, the New Model soldiers pursued the defenders through the streets, killing them as they ran. A group of defenders had barricaded themselves in Millmount Fort, overlooking the town's eastern gate held out while the rest of the town was being sacked. They negotiated a surrender, but were then disarmed and killed. Another group of soldiers in St Peter's church (at the northern end of Drogheda) were burned to death when the Parliamentarian soldiers set fire to the Church. Arthur Aston, the Royalist commander, was, reportedly, beaten to death with his own wooden leg, which the New Model Army soldiers thought had gold hidden in it. Richard Talbot, the future Jacobite Duke of Tyrconnell was one of the few members of the garrison to survive the sack. Only 150 Parliamentarians were killed in the attack. The few Royalists who survived were deported to Barbados. Cromwell wrote: "I do not think 30 of their whole number escaped with their lives. Those that did are in safe custody in the Barbados." Though Colonel John Hewson wrote "those in the towers being about 200, did yield to the Generals mercy, where most of them have their lives and be sent to Barbados.” The 200 taken prisoner tallies with Royalist estimates. It is alleged in some accounts that as few as 700 civilians died in the chaotic aftermath of the fall of Drogheda, though other accounts put this figure higher.
Cromwell justified the massacre at Drogheda in two ways. Firstly, he argued that it was, "the righteous judgement of God on these barbarous wretches, who have imbued their hands with so much innocent blood". In other words, his actions were justified in reprisal for the Irish massacre of English and Scottish Protestants in 1641. This was not a convincing argument however, as Drogheda had never fallen to the Irish rebels in 1641, or the forces of Confederate Ireland in the years that followed. The first Irish Catholic troops to be admitted to Drogheda arrived in 1649, as part of the alliance between the Irish Confederates and English Royalists. Drogheda had therefore never been held by those responsible for the massacre of Protestant civilians.
Secondly, he argued that such severity would discourage future resistance and save further loss of life. Cromwell's motivation was above all that he could not afford to have his army waste away in endless sieges and waste time. This may have worked up to a point, as towns like New Ross, Carlow and Kilkenny subsequently surrendered on terms when besieged by Cromwellian forces. Moreover, the Royalist commander, Ormonde wrote of the terrifying effect that Cromwell's army had on those under his command and how it was with difficulty that he could get them to act in their defence. On the other hand, such towns as Waterford, Duncannon, Clonmel, Limerick and Galway only surrendered after determined resistance, indicating that the terror Cromwell employed at Drogheda was not wholly effective in cowing Royalist morale.
Cromwell himself denied that his troops had killed civilians at Drogheda, but only those "in arms". Several recent analyses by historians have claimed that Cromwell’s orders were not exceptionally cruel by the standards of the day, which were that a fortified town that refused an offer of surrender, and was subsequently taken by assault, was not entitled to quarter. Tom Reilly, a local historian, has taken this a stage further, by also claiming that there was no evidence that unarmed civilians were killed on the streets of Drogheda - and that the stories of a massacre were the result of many years of unsubstantiated accounts from Royalists and later Irish Catholic clergy and Nationalists. But most professional historians accept that at least some of the town's civilians died in the sacking of Drogheda. A book review by Eugene Coyle in the magazine History Ireland dismisses Reilly's argument:
Historian Ian Gentles records in his book, the New Model Army that, "According to official estimates there were 3100 soldiers in the town, of whom 2,800 were killed, as well as many inhabitants and every friar that could be found. The final toll may thus have been... 3,500 soldiers, civilians and clergy". This would mean that of 3500 killed about 700 were civilians.