The 31-year-old will play Marcus, a survivor of a nuclear holocaust caused by the self-aware computer network system Skynet.
Worthington’s role will reportedly span three films as he becomes a central figure in the human fight against Skynet.
Christian Bale has already been cast as John Connor, the leader of the resistance. The role has previously been played by Edward Furlong and Nick Stahl on film and Thomas Dekker in TV series The Sarah Connor Chronicles.
Terminator Salvation director McG was recommended Worthington by James Cameron, the director of the first two franchise instalments.
Worthington will next be seen playing a paraplegic war veteran in Cameron’s Avatar, which is scheduled for a Christmas release next year.