Cheshire was a divided county in the first phase of the English Civil War. After the First Battle of Middlewich on 13 March 1643, Sir William Brereton's Parliamentarian forces held the eastern and central two-thirds of the county from their base at Nantwich, while the Royalists held the western portion, including the Dee Valley and the strategic port of Chester. Chester mattered because it was the disembarkation point for troops and supplies from Ireland and for recruits raised in North Wales. Through the summer of 1643 Brereton tightened the blockade around Chester, and in late October his forces temporarily cut the city off entirely by pushing into northern Wales. Charles I responded by appointing John, Lord Byron, to command Royalist forces in Cheshire and Lancashire, and in November Byron was reinforced by troops withdrawn from the Irish Confederate Wars and shipped across to fight for the King.

On 12 December 1643, Byron left Chester with 4,000 foot and 1,000 horse. He planned to capture Nantwich, clear Brereton out of the rest of Cheshire, and then move on Lancashire. The campaign that followed was unusually brutal even by the standards of a civil war. Byron took Beeston Castle on 13 December, and on 23 December his troops attacked the village of Barthomley, where the local schoolmaster and a handful of villagers had taken refuge in the church tower. The Royalists smoked them out by setting fire to the pews and rushes piled at the base, and twelve civilians were killed, including the schoolmaster. The massacre at Barthomley became one of the better-known atrocities of the First Civil War. It was committed in service of a military strategy that, for most of December, was working: Byron was sweeping aside Parliamentarian forces and capturing strongholds across central Cheshire.

On 25 December, Byron's army was camped at Sandbach, and Royalist sympathisers brought word that Brereton was deployed around Middlewich, about seven kilometres to the northwest. Brereton's scouts had been skirmishing with Royalist outposts. Both commanders moved quickly. Brereton was reinforced by 1,500 men under Colonel Alexander Rigby and deployed his forces along Booth Lane, placing infantry in the hedges and ditches that lined the road, cannon in the centre and cavalry on each flank. On the morning of 26 December, Byron marched his men the seven kilometres from Sandbach and attacked. The first hour was hand-to-hand fighting in the hedgerows, and despite their numerical advantage the Royalists could not break the Parliamentarian defences. Byron then sent in his cavalry, supported by infantry under Colonel Richard Gibson, and the Parliamentarians broke. The survivors took refuge in houses and the church; two hundred men were left dead on the field. Brereton himself rode northwest with what remained of his army, toward Manchester.

The inhabitants of Middlewich came out of their houses and onto the field to attend to the wounded and bury the dead. The town itself was ransacked, food and valuables carried off, and within weeks plague broke out for the second time in living memory. The trauma of the battle was woven into the trauma of disease, and the town did not recover quickly. Some of the dead were Parliamentarian soldiers from distant counties, others were locals; some had been pressed into service, others had volunteered for one side or the other for reasons that ranged from religious conviction to family loyalty to the simple need for pay. Civil wars are wars where neighbours kill neighbours, and the dead on Booth Lane included men whose families lived within a day's ride.

Byron's victory at Middlewich opened the rest of central Cheshire to the Royalists. Over the following weeks he took the Parliamentarian garrisons at Northwich, Crewe Hall and Doddington Hall, before attacking Nantwich itself on 18 January 1644. Nantwich, however, held. The town was defended by a well-equipped Parliamentarian garrison of 1,500 men, and Byron was repulsed with heavy casualties. While the siege dragged on, Brereton was reinforced by Parliamentarian troops from Yorkshire under Sir Thomas Fairfax, and on 25 January 1644 the combined Parliamentarian armies defeated Byron at the Battle of Nantwich. Byron retreated into Chester and stayed there, by and large, for the next two years. The county returned to Parliamentarian control, and Chester itself would not finally surrender until February 1646. The Royalist successes of December 1643, including the victory along Booth Lane, had lasted barely a month.