The former Jag star will portray the Hollywood Western icon in Trumbo, alongside Breaking Bad's Bryan Cranston, who will take on the titular role.
The film will tell the story of the Oscar-winning screenwriter, who penned 1960 epic Spartacus and Paul Newman's classic Exodus.
He became a Hollywood outcast in 1947 after he refused to testify in front of the U.S. Congress during an investigation of Communist influences in the movie industry and was sent to prison in 1950 for contempt.
Acting legend Wayne was president of the Motion Picture Alliance for the Preservation of American Ideals, the organisation which gave the names of Hollywood's questionable celebrities to Congress.
Trumbo, which will be directed by Meet the Fockers' Jay Roach, also stars Dame Helen Mirren, Diane Lane and John Goodman.