That year, he had his first artwork, a drawing of Malmesbury Abbey, accepted for exhibition at the Royal Academy. John Britton soon began training the young Samuel Rayner as an architectural draughtsman, taking him on sketching trips around the country and making intricate sketches of buildings and monuments. It was whilst training under John Britton that Rayner met the artist George Cattermole, who would become a close friend and influence on his career.

On 2 October 1823, Samuel Rayner married Ann Manser, the daughter of William Manser, a successful London publisher. The couple had eloped, as Rayner was just seventeen at the time and Ann was four years his senior, and it was likely that his prospective father-in-law did not approve of his daughter marrying a younger man with, at the time, limited prospects. The couple settled at 11 Blandford Street, a few doors from his family business. In 1826, they welcomed their first child, Ann, who would be known throughout her life as Nancy. Ann Manser was also an artist and engraver in black marble and in 1827 they exhibited together two drawings of Westminster Abbey at the Royal Academy. That same year, Samuel Rayner came into a considerable amount of money, through an inheritance from his grandfather’s estate, and a significant commission from William George Spencer Cavendish, the sixth duke of Devonshire at Chatsworth. This change in financial circumstances inspired Rayner to move his family to Museum Parade in Matlock Bath, where he started a business as a publisher and printer. In 1830, he published Rayner’s Sketches of Derbyshire Scenery Part 1 before, in 1833, the family returned to London, possibly due to the poor health of Rayner’s mother. By this time, Samuel and his wife had had four more children, Rhoda (1828), William Harry (1830), Louise (1832) and Samuel (1833). Rayner’s mother died in 1834 and later that year, the couple welcomed their fifth child, Frances. In 1836, the family returned to Derby, moving his business to 17 Friar Gate and publishing History and Antiquities of Haddon Hall. Back in Derbyshire, Samuel and Ann would have two more children, Margaret (1837) and Dorothy (1839). In 1842, the family once again returned to London, settling on Berners Street, near Oxford Circus. The following year, they had their ninth and final child, Richard. In 1845, Samuel Rayner was elected an associate of the Society of Painters in Water Colours, and he would exhibit 29 drawings there between 1845 and 1850.

In 1851, Rayner’s relationship with his family and reputation came under severe strain when his father-in-law, William Manser, was charged with fraud and Samuel was implicated. The case alleged that Manser had written a promissory note for the sum of £2,000 to Rayner’s daughter Nancy, which Rayner had used to make a payment to a Mr Roe, and so endorsed the note to pass the rights to him. When the payment was later refused, Rayner’s father-in-law claimed that the note was not genuine and his signature was a forgery. The court ruled against Manser and despite there being no proof of wrongdoing on the part of Rayner, a belief persisted that he had been colluding with his father-in-law in an attempt to default on the payment. A unanimous vote expelled him from the Society of Painters in Water Colours and he spent the rest of his career exhibiting in provincial galleries and away from the more prestigious London galleries. The family lived at various addresses around London and, between 1859 and 1864, in Brighton. In his final years, Samuel Rayner lived in Windsor, where he died on 19 August 1879. He was survived by his wife and nine children. His son Richard and five of his daughters, Nancy, Rhoda, Frances, Louise and Margaret, all became professional artists.