Romney first conceived of painting Milton in 1790 as part of a series of four works depicting iconic cultural figures from English history. The other three were to have been Newton, Christopher Wren and Francis Bacon. This set was never executed, with the artist instead commissioned in late 1791 or early 1792 to create a painting that would be used to illustrate an edition of Milton's works, as well as for a biography to be written by William Hayley and published by John and Josiah Boydell as a follow-up to their Shakespeare Gallery.

The completed painting shows the blind Milton seated to the right of the canvas, legs crossed in front of him. Romeny cleverly combined separate episodes in the poet's life in the figures of his daughters, seated to the left with their heads bent together. The first daughter, probably intended to be Deborah, his favourite, is reading to her father. According to Hayley, she was so dedicated to her father that at his request she would read to him in languages she did not even understand. The second daughter is shown transcribing Paradise Lost as her father dictates.

There are several preliminary sketches that show the evolution of the artist's concept of the picture in three sketchbooks: two dating to August 1792 (the first with Anthony Mould, London, 2000 and the second Princeton) and one to October 1792 (Huntingdon). Romney chiefly experimented with the position of Milton; the sketchbooks include drawings of the figure in the position seen in the present brunaille sketch. It is not clear if it was the artist or his patrons who decided against the more theatrical pose, with the poet's leg hooked over the arm of his chair in favour of the more solemn final position. The oil sketch has been executed over the top of an abandoned three-quarters portrait of a gentleman that can still be made out to Milton's left.