His publicist, Max Clifford, said he died in the arms of his wife, actress Susan George, on Thursday night in a London Clinic.
The actor revealed last year he was diagnosed with bowel cancer in 2006, but was told it was terminal after it spread to his lungs a year later.
He spent six years on the BBC medical drama as Dr Harry Harper.
He was also known for starring in 1980s series Manimal and appearing in the 1978 Agatha Christie film Death on the Nile.
"He fought it with such strength, courage and belief. Last night, he lost this battle, and he died peacefully in my arms.
"To me, he was simply the best of everything, and I loved him with all my heart. He will live on in me forever."
Born in Cambridge, MacCorkindale intended to follow his father into the RAF, but his deteriorating eyesight meant he had to follow an alternative path.
He began his career in theatre, making his West End debut in a production of Pygmalion, before moving to the small screen.
He moved to the US after the success of Death on the Nile where he had roles in various TV series including Dynasty, Hart to Hart and The Dukes of Hazzard before securing the lead in adventure series Manimal.'Amazing energy'
After being diagnosed with cancer while working on Casualty, he left the drama and returned to the stage in the West End production of The Sound of Music until its closed in February 2009.
His last television appearance was on BBC series New Tricks earlier this year.
John Yorke, controller of BBC drama production, said the actor was owed a "massive debt" for his work in Casualty.
"Not only was he a fabulously iconic consultant, he was also an inspirational team leader," Mr Yorke said.
"One of the reasons so many people have loved working with him on Casualty is because of the tone he established on the shop floor - always welcoming, always disciplined, always quietly the leader.
"Simon had an extraordinary career encompassing - amongst many other things - matinee idol, Hollywood lead, film and theatre director, film producer and horse breeder.
"That amazing energy and appetite for life remained with him to the end."
Simon will be missed!