A land surveyor turned engraver, Boydell began early in his career to publish his own prints, chiefly of English views he himself drew. This led him to publish the works of other engravers, and after about 1767 he devoted himself entirely to the publishing and selling of engravings.

Up until this time, most of the prints for sale in England were imported from the European continent, particularly France. The French publishers, however, would not exchange credit to or exchange prints with the English dealers, and demanded to be paid in cash. This prompted Boydell to commission English engravers to execute plates after English paintings, thereby competing with France on an equal level. The resulting works were the first English prints to ever be in demand in Europe.

Boydell became quite wealthy, but he chose to spend most of the fortune he made from print publishing into promoting the arts through the commission of both the engravings and the paintings these were taken from, as well as the physical development of the Shakespeare Gallery. In his later years, he was awarded civic honors for his patronage of the arts: in 1782 he became alderman of London, a post he held until his death; in 1785 he was made sheriff of the city, and then he served as Lord mayor for the year 1790/1791. Although the idea of the Shakespeare Gallery was not his own, but that of his nephew, artists, and friends, he expressed the desire to carry out the project. His money, influence, and experience made it a reality. The Shakespeare Gallery ran into financial difficulties and Boydell chose to offer it up through a lottery as a way to pay his creditors. However, Boydell never saw the disbanding of the collection actually take place. He died on December 1804, a month before the lottery took place.