His firm published works by a range of noteworthy authors, including Hall Caine, Lewis Carroll, Arthur Conan Doyle, Charles Darwin, Thomas Henry Huxley, Herbert Spencer, and John Stuart Mill, as well as leading American scientists and philosophers of his era.

His grandson, through his son William, was William Henry Appleton (1866–1951),[13][14] a prominent yachtsman who married Noel Johnston, granddaughter of John Taylor Johnston, former president of the Central Railroad of New Jersey and the founding president of The Metropolitan Museum of Art.

[6] Appleton City, Missouri, was named after the publisher, in appreciation of his 1870 donation to the town's library.

[15] Appleton is a character in the time travel novel The Plot to Save Socrates by Paul Levinson.

As depicted in the book, Appleton had an extensive secret life as a time-traveler, had visited Classical Greece and met in person some of the famous ancient Greek writers and philosophers whose works he published, and also several times visited the 21st century – but always found his own 19th century milieu to be the most congenial.