Cloud Atlas

In 2005, while on the London set of V for Vendetta (2005), Natalie Portman gave a copy of the original novel to Lana Wachowski, who became deeply interested in it. A year later, both Wachowski siblings wrote a first draft of the screenplay. Tom Tykwer, a friend of the Wachowskis, was invited to co-author several subsequent drafts with them in the following two years, constantly keeping in mind observations by the book's author himself, David Mitchell, while looking for international investors. In all those years, Portman was promised the role of Sonmi-451, but had to turn down the role at the last minute after becoming pregnant in 2010; however, she is given a special thanks in the closing credits.

The 1849 slave trade contract that Ewing was bringing back to his Father in the states was unenforceable. The slave trade had been outlawed in the United States on January 1, 1808, the first date permitted by the Constitution. The Act Prohibiting Importation of Slaves of 1807 (2 Stat. 426, enacted March 2, 1807). Slaves could no longer be imported into the United States. The slave trade was dead. Likewise, California was a "free state" where owning slaves was outlawed in 1849.

When a montage is shown of all the characters the actors play, the font of the names changes with each time period.

The 2025 Shout Factory 4K and Blu-ray have corrected the end credits to reflect Lilly Wachowski's transition.