The Clemens family had it designed by Edward Tuckerman Potter and built in the American High Gothic style.

[6] The Panic of 1893 further threatened their financial stability, and Clemens, his wife Olivia, and their middle daughter, Clara, spent the year 1895–96 traveling so that he could lecture and earn the money to pay off their debts.

In 1929, it was rescued from possible demolition and put under the care of the newly formed non-profit group Mark Twain Memorial.

In 2003, a multimillion-dollar, LEED-certified visitors' center was built that included a museum dedicated to showcasing Twain's life and work.

[8] The house faced serious financial trouble in 2008 due partly to construction cost overruns related to the new visitors' center,[9] but the museum was helped through publicity about their plight, quick reaction from the state of Connecticut, corporations, and other donors, and a benefit performance organized by writers.

[12] It has featured events such as celebrity appearances by Stephen King, Judy Blume, John Grisham, and others; it has also sponsored writing programs and awards.

[21] The home is in the style of Victorian Gothic Revival architecture, including the typical steeply-pitched roof and an asymmetrical bay window layout.

[21] He also hosted several authors as guests, including Thomas Bailey Aldrich, George Washington Cable, and William Dean Howells, as well as actors Henry Irving, Lawrence Barrett, and Edwin Booth.

[28] Clemens worked on many of his most notable books in this home, including The Adventures of Tom Sawyer (1876) and Life on the Mississippi (1883).

[24] The success of The Adventures of Tom Sawyer inspired him to renovate the house, and he had Louis Comfort Tiffany supervise the interior decoration in 1881.

[24] He also formed the firm Charles L. Webster & Company, which published Twain's own writings, and issued a bestseller with Ulysses S. Grant's memoirs.

[24] The losses from these investments as well as several bank panics led the Clemens family to move to Europe in 1891 where the cost of living was more affordable.

It is the loveliest home that ever was.”[33] Katharine Seymour Day was a grand-niece of Harriet Beecher Stowe who had known the Clemens family, and she saved the Twain House from destruction in 1929.

[34] It took many decades to pay off the mortgage and raise money to restore the deteriorating property, as well as to retrieve artifacts, furnishings, and personal possessions.

[37] The house underwent a major renovation starting in 1999, including work on the exterior wood, tile, and terra cotta brick, and rebuilding the purple slate roofs.

The marble floor in the front hallway underwent a historic restoration, and specialists re-stenciled and painted the walls and ceilings and refinished the woodwork to recover the Tiffany-decorated interiors.

Many of the original furnishings remain at the house, including the Clemens' ornate Venetian bed, an intricately carved mantel from a Scottish Castle and a billiard table.

[44] The National Endowment for the Humanities gave $800,000 in challenge grants for teacher development programs, a student writing contest, and an educational website.

[45] After building the Visitors Center in 2003, the house became financially unsustainable and launched a campaign to raise awareness and funds.