The actors, who played Liam Murphy and Romeo Smith respectively, have already filmed their final scenes for the Summer Bay drama, TV Week reports.
Departure storylines for the pair are expected to air in 2013, while both cast members have been tipped to look for career opportunities in the US in the coming months.
Whitehead has been appearing in the role of Liam since early 2009, while Mitchell made his debut as Romeo a few months later.
News of Mitchell's exit comes just a few months after his real-life fiancée Rebecca Breeds was seen bowing out as Ruby Buckton.
Home and Away airs weekdays at 1.15pm and 6pm on Channel 5 in the UK, and weekdays at 7pm on Network Seven in Australia.