Nicholl was born in Belfast, the son of a shoemaker. He was a self-taught artist who appears to have been encouraged by his brother William, a business man and amateur artist. He was late to take up a career as an artist working first as a compositor for the printer F.D. Finlay on the newspaper the Northern Whig. He had already gained local recognition as an artist when in 1830 he travelled to London where his style developed under the partronage of Emerson Tennent. Nicholl spent time copying Old Masters at the Dulwich Picture Gallery where his favourite artists were Cuyp, De Wint and Copley Fielding. It was at Dulwich that he also saw his first works by Turner, an artist who remained a major influence throughout his career.
From 1832 he exhibited at the Royal Academy and the Royal Hibernian Academy, of which he was elected an Associate in 1837 and a full member in 1860. In 1846 Nicholl was sent to Ceylon to take up the post of drawing master at the Colombo Academy. On his return he lived in Belfast and London and made frequent visits to Dublin.
The first mention of Nicholl's flower paintings is in a sonnet written in 1830 by his patron Emerson's sister, Eliza. His watercolours are usually composed with microscopically detailed wild flowers and accurately observed topography beyond. Nicholl used Turner's technique of scratching out to highlight his foliage and also John Glover's split brush technique.