Brunner and Mond decided to build their factory at Winnington, near Northwich, Cheshire on land owned by Lord Stanley of Alderley. This was sited on the River Weaver which allowed for the transport of the raw materials and finished products to and from the works. Lord Stanley insisted on selling the house, Winnington Hall, as well as the surrounding land, as part of the deal. The purchase was completed in 1873, and for a time both Mond and Brunner lived separately in the wings of the hall. The early years were extremely difficult, initially in getting the plant to work efficiently and then in selling the soda ash. It was not until 1878 that success was achieved when they outsold their competitors and were producing their products more cheaply. In 1881, the partnership was converted into a limited company with capital assets listed at £600,000 and the founders became managing directors for life. In 1891, Brunner became the chairman and retained that position until April 1918, 14 months before his death. However by then his duties were being increasingly performed by his son, Roscoe.
After its slow start, Brunner Mond & Company became the wealthiest British chemical company of the late 19th century. On its merger with three other British chemical companies to form Imperial Chemical Industries (ICI) in 1926, it had a market capitalization of over £18 million. Brunner's sobriquet, "Chemical Croesus", was given to him by The Times. He was a paternalistic employer and went to great lengths to improve the situation of his employees. Measures introduced by Brunner and Mond were shorter working hours, sickness and injury insurance, and holidays with pay.
During the years he was working at Hutchinson's in Widnes, Brunner was developing his political interests. He joined the Widnes chapter of the National Education League and became its secretary in 1872. This gave him the opportunity to come into contact with Liberals from Liverpool and other parts of the country. Soon after moving to Northwich Brunner became more practically involved with education locally, in particular with the British School in the town. He later served on its board of governors and also on the local sanitary authority. As a result of the Redistribution of Seats Act 1885 the parliamentary constituency of Northwich was created and Brunner offered himself as a candidate for the Liberal Party. In his speech for the position he expressed support for the disestablishment of the Church of England, for reform of property laws, for Irish Home Rule and for compensation for those whose properties had been damaged by the pumping of brine from the salt mines in the area. During the campaign he was heckled because he had a foreign-sounding name. He responded "My father was a Swiss, my mother was a Manx woman, I was born in Liverpool, my nurse was Welsh: is that Cheshire enough for you? At the general election on 1 December 1885 Brunner beat William Henry Verdin, his Conservative rival, with a majority of 1,028.
The Liberal Party won more seats than any other party in the election, but insufficient to form a majority government, leaving the Irish Parliamentary Party holding the balance of power. It proved impossible to form a stable government, and so another general election was called in June 1886. In the meantime, the Liberal Party had split, and the Liberal Unionist Party had been formed. Brunner's opponent at the 1886 election was William Henry Verdin's brother, Robert, standing as a Liberal Unionist. The election was held on 13 July 1886, and Brunner was defeated by 458 votes. In November 1886, Brunner embarked on a world tour, accompanied by his wife and his son Stephen. His return to Northwich on 2 July 1887 was greeted with great celebration, as he was extremely popular in the town, regarded as a kind and sympathetic employer and a generous benefactor. Within three weeks of Brunner's return, Robert Verdin died and a by-election was called. Brunner's opponent was Lord Henry Grosvenor, who was standing as a Liberal Unionist. This time, at the election on 13 August, Brunner won with a majority of 1,129. At the 1892 general election, Brunner's opponent was not a Liberal Unionist, but a Conservative, George Whiteley, who was a cotton manufacturer from Blackburn. Brunner was returned with an increased majority of 1,255. In the 1895 election he beat Thomas Ward, another Conservative, by 1,638 votes. The 1900 general election was held during the Boer War, to which Brunner was opposed. He retained his seat, but with a reduced majority of 699. In the 1906 general election, Brunner's opponent was the Conservative Colonel B.N. North who had fought in the Boer War. Brunner increased his majority to 1,792. He continued to be the Member of Parliament for Northwich until the general election in January 1910, when he decided not to stand again, partly because of his own health and also because of concern for his wife's health. Subsequently he moved to Surrey, but continued to play a part in politics when he was elected to the Chertsey division of Surrey County Council.
As a Liberal MP he supported Irish Home Rule, trade unions, free trade and welfare reforms. Leading up to the First World War he argued that Britain should adopt a more sympathetic approach towards Germany, including naval disarmament. When war did break out, Brunner was resolute in the opinion that it should be fought and won. In addition to the production of alkali, his factories were making other chemicals for use as explosives. He also built a new factory to purify trinitrotoluene.
Abroad he gave gifts to the Landesmuseum in Zürich and provided a hospital, also in Switzerland. In 1885 he became a Freemason and in 1900 founded the John Brunner Lodge at Over Winsford. The following year he was honoured with the brevet rank of Past Grand Deacon of England.
In 1899 Brunner (who had by then been created a baronet) became chairman of the Runcorn and Widnes Transporter Bridge Company. He subscribed £25,000 towards its construction plus a loan of £12,000 together with a personal guarantee on a bank loan of £31,000. When the building of the bridge was complete in 1905 it was due to be opened by Edward VII, but the king was unable to attend, and so Brunner performed the ceremony himself. By 1911 it had become apparent that the bridge would always operate at a loss, and Brunner assigned his interest in it to Widnes Corporation. The Times stated that this action amounted to a "virtual gift of £68,000".
Amongst other offices held, he was Vice-President of the British Science Guild, Deputy Lieutenant for the County of Lancashire and Pro-Chancellor of the University of Liverpool. In 1909 the University of Liverpool awarded him the honorary degree of Doctor of Laws. In 1895 he was made the Baronet of Druids Cross in the County of Lancashire and in 1906 he became a member of the privy council, but he declined offers of a peerage. He died in 1919 at his home in Chertsey, Surrey. His estate amounted to over £906,000 and in addition he had given generous amounts of money to his five married daughters and had transferred investments to his sons. The baronetcy passed to his eldest son, John Fowler Leece Brunner.