In 1609, King James I granted Sir Fulke Conway, a Welshman of Norman descent, the lands of Killultagh in southwest County Antrim. By 1611, George Carew was reporting that Conway had built a fine timber house and a bridge across the Lagan and was planning a fortified bawn at a place called Lisnagarvagh - the original name of Lisburn. Management of the estate fell to a Yorkshire man named George Rawdon, who laid out the streets that still define the town: Market Square, Bridge Street, Castle Street, Bow Street. Rawdon built a church on the site of today's cathedral in 1623. In 1628, Charles I granted the town a charter for a weekly Tuesday market that has never lapsed. Rawdon was hostile to the Scots Presbyterians already settling in the area and brought English and Welsh tenants instead. The community he created became loyalist, industrial, and Anglican by design.

Linen had been brought to Ireland by Scots, but it was the arrival of Huguenot refugees in 1698 that turned Lisburn into the industry's capital. Driven from France by religious persecution, they brought sophisticated weaving techniques and government support. The Crown gave Louis Crommelin, overseer of the royal linen manufacture of Ireland, money to promote production. The Huguenots kept their own French Church in Castle Street until 1820. Industrial scale arrived in 1764 when William Coulson set up linen looms near what is now Union Bridge. His mill supplied damask to royal courts across Europe - Russian grand dukes, Swedish crown princes, the Duke of Wellington all came to inspect. In 1784 a Scotsman named John Barbour began spinning linen thread, and by the end of the nineteenth century his son's Hilden mill was the largest linen-thread factory in the world, employing two thousand workers.

On 22 August 1920, as worshippers left Sunday service at Lisburn Cathedral, the IRA assassinated RIC Inspector Oswald Swanzy in Market Square. Swanzy had been named at a Cork inquest as responsible for the killing of Tomás Mac Curtain, the city's republican Lord Mayor. Over the next three days, Protestant loyalist crowds looted and burned almost every Catholic business in Lisburn and attacked Catholic homes. Ulster Volunteers helped organise some of the burnings. Rioters attacked firefighters and British soldiers sent to help. About a thousand people - a third of Lisburn's Catholic population - fled, many taking the mountain road to Belfast where worse was about to come. A pub owner died of gunshot wounds. About thirty special constables were charged in October; the charges were not pursued. The Burnings became a template for the violence that consumed Belfast in the partition months that followed.

Through the twentieth century the linen industry slid into long decline. New synthetic textiles, changing fashion, and global competition reduced what had been the engine of the town. The Hilden mill that the Barbours built closed in 2006 with a workforce of just eighty-five, down from two thousand at its peak. The M1 motorway, opening in 1962, integrated Lisburn into the Belfast commercial area. The Sprucefield retail park opened in 1989 and was devastated by an IRA incendiary attack in January 1991 - Marks and Spencer, the anchor tenant, was spared, but three other stores were destroyed. Lisburn became a city during Queen Elizabeth II's Golden Jubilee in 2002. Lagan Valley Island, on what was once Vitriol Island where bleach was produced, opened as a civic complex in 2001. Twelve percent of the working population still works in manufacturing - precision engineering rather than woven flax.

First built in 1940 and named after a Somme battlefield where the Ulster Division suffered its heaviest losses in 1916, Thiepval Barracks remains the British Army's Northern Ireland headquarters and home to 38 Irish Brigade. Two IRA car bombs killed a soldier and injured 31 inside the barracks on 7 October 1996 - among the last casualties of the Troubles in the town. The 2024 UK general election returned Sorcha Eastwood for the Alliance Party in Lagan Valley - the first time the constituency had returned a non-unionist, a woman, or a candidate from a Catholic community background. In June 2023, Gary McCleave became the first Sinn Féin councillor to hold a mayoral position in Lisburn and Castlereagh, serving as deputy mayor. The Latin motto still reads Ex igne resurgam. The town has had a lot of fires to rise from.