Karl Queensborough is to take over the title role in Hamilton from Jamael Westman, who has starred in the show since it opened in London.
Queensborough currently performs as the alternate Alexander Hamilton, but will play the part full time from November 18.
Trevor Dion Nicholas, who played Genie in the West End production of Aladdin, will join the cast as George Washington, while former Kinky Boots star Simon-Anthony Rhoden has been cast as Aaron Burr.
Gavin Spokes will take over the role of King George from November 4, while Nuno Queimado will play the role of Hamilton at certain performances from the same date.
Allyson Ava-Brown and Jason Pennycooke continue in their roles, and lead casting is completed by Emilie Louise Israel, Sharon Rose, Emile Ruddock and Carl Spencer.
The show, which enters its third year at the Victoria Palace Theatre in December, is now booking until March 28, 2020.
Hamilton is written by Lin-Manuel Miranda, directed by Thomas Kail and choreographed by Andy Blankenbuehler.
It is produced in the West End by Jeffrey Seller, Sander Jacobs, Jill Furman, the Public Theater and Cameron Mackintosh.