[4] In the early years Little and Brown published the Works of Daniel Webster, George Bancroft's History of the United States,[3] William H. Prescott's Ferdinand and Isabella, Jones Very's first book of poetry (edited by Ralph Waldo Emerson), Letters of John Adams and works by James Russell Lowell and Francis Parkman.

[1][3] The firm was the original publisher of United States Statutes at Large beginning in 1845, under authority granted by a joint resolution of Congress.

In 1874, Congress transferred the authority to publish the Statutes at Large to the Government Printing Office, which has been responsible for producing the set since that time.

Other prominent figures published by Little, Brown in the 20th and early 21st centuries have included Nagaru Tanigawa, Donald Barthelme, Louisa M. Alcott, Catherine Drinker Bowen, Bernie Brillstein, Thornton Burgess, Hortense Calisher, Bruce Catton, A. J. Cronin, Peter De Vries, J. Frank Dobie, C. S. Forester, John Fowles, Malcolm Gladwell, Pete Hamill, Cynthia Harrod-Eagles, Lillian Hellman, Oliver Wendell Holmes Sr., Henry Kissinger, Elizabeth Kostova, Norman Mailer, William Manchester, Nelson Mandela, John P. Marquand, Masters and Johnson, Stephenie Meyer, Rick Moody, Ogden Nash, Edwin O'Connor, Erich Maria Remarque, Alice Sebold, David Sedaris, George Stephanopoulos, Gwyn Thomas, Gore Vidal, David Foster Wallace, Evelyn Waugh, John A. Williams, P. G. Wodehouse, James Patterson and Herman Wouk.

In 2001, all editing staff moved from Boston to Time Warner Book Group offices in New York City.

Little, Brown expanded into the United Kingdom in 1992 when TWBG bought MacDonald & Co from Maxwell Communications, taking on its Abacus (upmarket paperback) and Orbit (science fiction) lists, and authors including Iain Banks.

Also in 1996, Wolters Kluwer acquired Little, Brown's legal and medical publishing division and incorporated it into its Aspen and Lippincott-Raven imprints.

[14] The imprint Little, Brown Spark launched in fall 2018[15] and has published authors such as Mark Hyman, Tricia Hersey, and Sue Johnson.

In October 2018, Little, Brown announced an imprint dedicated to illustrated books with Michael Szczerban as vice president and editorial director.

[16][17] The Voracious imprint launched in fall 2019[18] and has published works by Accidentally Wes Anderson, Ayesha Curry, Vivian Howard, Christopher Kimball's Milk Street, Marcus Samuelsson, and Pete Souza, among others.