They never returned.
The Inuit, native residents of the North, tell tales of the three-masted ships caught in ice and of men afflicted by scurvy and going hungry, until finally they broke the biggest taboo of humankind: cannibalism.
It was not until 2014 that the first traces of the expedition emerged, when divers located a shipwreck that they identified as HMS Erebus, named after the spiritual limbo between Earth and hell.
Last month, the second big piece of the mystery fell into place when an Inuit ranger and a team of explorers announced that they had located HMS Terror - in near-pristine condition, not far from the Erebus - at the bottom of the Northwest Passage.
The story of the ships' loss and eventual finding reveals how much the Arctic, and our relationship with this frontier, has changed in just a few decades.
The ice is no longer what it once was; scientists think that the Arctic will be reliably ice-free and navigable in the summer by the middle of the century, if not earlier.
The admiralty asked John Franklin, a 59-year-old polar explorer, to find a northern sea path linking the Atlantic and Pacific oceans.
Europeans thought of the world as perfect and symmetrical, according to Franklin's Lost Ship, a book by John Geiger and Alanna Mitchell.
Explorers had discovered a passage at the bottom of South America that linked the Atlantic and the Pacific. And so people reasoned that a similar one must exist in the north.
He filled his hold with three years' worth of canned food in case the voyage took longer than the expected two years.
On May 19, 1845, Erebus and Terror, both painted a menacing black with a yellow stripe, set off down the River Thames and into the Atlantic Ocean. Londoners thronged the banks and cheered the might of their empire.
But Franklin was heading into a frontier that science had not mastered.
Compasses did not work properly because their magnetic readings were impaired by proximity to the North Pole. There were no weather reports. It was much colder than today, and there were years with no summer ice melt at all, said Ryan Harris, an underwater archaeologist at Parks Canada.
Ships can quickly get trapped in cement-like ice.
TRAPPED BY ICE
The expedition entered the Arctic Ocean before the end of May and picked through the labyrinth of the Canadian Arctic archipelago.
Franklin and his men reached as far north as 77 degrees, about 1368km from the North Pole, before wintering on a tiny uninhabited island.