At the age of fifteen Louise began to study painting seriously, at first with her father, and later with George Cattermole (1800-1868), Edmund Niemann (1813-1876), David Roberts (1796-1864) and Frank Stone (1800-1859). Roberts, the best known of the four, was a Scottish artist who specialised in architectural and topographical scenes. He trained as a stage scenery painter before travelling through France and Spain, where he made dramatic and evocative pictures of churches, ruins and cities. From 1838 he travelled throughout the Middle East recording the Holy Land. His influence can be seen in Louise Rayner’s later works. Her first exhibit at the Royal Academy in 1852 was an oil painting of "The Interior of Haddon Chapel, Derbyshire".

Louise Rayner, like Roberts, depicted cities and ruins as well as stately homes and their surroundings. Louise is first recorded as being in Chester in 1869, by which point she had reached her mature style. Her paintings from this period are very detailed and highly picturesque, capturing the "olde worlde" character of Chester and other cities. She often filled her most finished works with figures going about their daily tasks, including street sellers and purchasers. Louise travelled extensively throughout Britain each summer during the 1870s and 1880s, and also visited northern France. Her watercolors include scenes of Edinburgh, Shrewsbury, Gloucester, York, London, Coventry, Windsor and Salisbury.