Midleton is a Williamite town. After the Battle of the Boyne in 1690, the new Protestant order in Ireland rewarded its supporters with land and influence, and the Brodrick family became one of the dominant houses of East Cork. Alan Brodrick - Speaker of the Irish House of Commons, then Lord Chancellor of Ireland - was made Baron Brodrick in 1715 and Viscount Midleton in 1717. The town took his title, more or less, as its English-language name. The fine Market House on Main Street, completed in 1789, served the cattle and butter trade of East Cork for two centuries before being converted to the Midleton Library, which it remains. Two houses at the bottom of Main Street were designed by Augustus Welby Pugin, later the architect of the Houses of Parliament in London; they have since been knocked together into a single building that operates as a public bar.

In 1825 James Murphy built a distillery on the southern edge of Midleton, set against the Owenacurra River so its great water wheel could turn day and night. The Old Midleton Distillery operated independently until 1868, when it merged into the Cork Distilleries Company. A century later, in 1966-67, the Cork Distilleries Company joined Jameson and Powers to form Irish Distillers, and they decided to consolidate everything in a brand-new plant built right next to the old one. The Old Midleton Distillery closed in 1975. Inside it sits the largest pot still ever made - 31,618 gallons, big enough that the still-room walls were assembled around it. Its working water wheel, seven metres across, is the largest in Ireland. The Old Distillery is now the Jameson Experience, a visitor centre; the New Midleton Distillery beside it produces Jameson, Powers, Paddy, Midleton Very Rare, Redbreast, Green Spot and most of the whiskies that the world thinks of as Irish.

At the top of Main Street stands a monument to sixteen men of the Irish Republican Army killed on 20 February 1921 during the War of Independence. The Clonmult Ambush, named for a village a few kilometres northwest of Midleton, was the worst single defeat the IRA suffered during that war. A flying column had taken shelter in a farmhouse when British forces - the Hampshire Regiment, supported by the Auxiliaries - surrounded them and set the building on fire. Twelve IRA men were killed in the engagement, and four of the survivors were captured. Two of those captured were later executed by firing squad. The monument lists all sixteen names. Local memory of Clonmult remained sharp for generations; even now, the names cut into the stone serve as a register of a community that lost more than its share of its young men in one bad February afternoon.

In Bailick Park, on the edge of the town, stands a sculpture of nine large stainless-steel eagle feathers arranged in a circle, leaning inward as if forming an empty bowl. It is called Kindred Spirits, the work of the Cork-born sculptor Alex Pentek, and it was unveiled in 2015. The bowl shape is a thank-you. In 1847, at the worst moment of the Great Famine, the Choctaw Nation of what is now Oklahoma - a tribe that had itself been forced west on the Trail of Tears just sixteen years earlier - took up a collection of $170 and sent it to Famine relief in Ireland. The money was a great deal more than the small, impoverished nation could afford. The sculpture in Midleton is the formal Irish acknowledgement of a kindness held in memory for a century and a half. In 2020, when the Navajo Nation and Hopi Reservation needed COVID-19 relief, Irish donors gave back, citing the Choctaw gift by name. The line of gratitude runs both ways now.

The flat valley that made Midleton an easy place to ford the Owenacurra also makes it easy to flood. On 30 December 2015, Storm Frank sent the river over its banks and into Main Street; businesses in the town centre were knee-deep in brown water for days. In October 2023, Storm Babet did much the same, on a worse scale - the worst flooding in the town's modern history, with hundreds of homes and businesses affected. Between those two storms Midleton has roughly doubled in population. The 1996 census recorded 6,209 people; the 2022 census recorded 13,906. The population grew partly because of expansion of the distillery and food-processing plants; partly because of commuting distances to Cork city, sixteen kilometres west by the N25; and partly because Cork-area house prices pushed young families out into the East Cork market towns. Among the modern residents have been the Oscar-nominated animator Nora Twomey, who co-founded the celebrated Cartoon Saloon studio.