After having learned to weave, Rylands became a small-scale manufacturer of hand-looms, while also working in the draper's shop which his father had opened in St Helens. He displayed a "precocious shrewdness" for retailing, and in partnership with his two elder brothers expanded into the wholesale trade. So successful were they that, in 1819, Rylands' father merged his retail business with theirs, creating the firm of Rylands & Sons. At its peak, the company employed a workforce of 15,000 in 17 mills and factories, producing 35 tons of cloth a day.
His aptitude for trade quickly became obvious and manifested itself early and, before the age of eighteen, he entered into partnership with his elder brothers Joseph and Richard. Their father joined them in 1819, when the firm of Rylands & Sons was established, the seat of operations being established in Wigan. Their manufactures for some years consisted of ginghams, checks, ticks, dowlases, calicoes and linens.
John, the youngest partner, occupied himself with travelling over several counties for orders until 1823, when he opened a warehouse for the firm in Manchester. Business increased rapidly, and in the course of a few years extensive properties at Wigan, along with dye works and bleach works, were purchased. Valuable seams of coal were afterwards discovered under these properties, and proved a great source of wealth to the purchasers.