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 businessman 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 under the patronage of Emerson Tennent. Nicholl spent time at Dulwich picture gallery where he 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 was elected Associate in 1837 and a full member in 1860.
The first mention of Nicholl's flower paintings was written in 1830 by Emerson Tennent's sister, Eliza. His watercolours are composed of microscopically detailed wild flowers often with topographical views beyond. Nicholl used Turner's technique of scratching out to highlight his foliage and also John Glover's split brush technique.