During his time at the long-running ITV1 arts show, Cain directed films about a wide variety of personalities, including artist Sam Taylor-Wood, dancer Darcey Bussell and actor Michael Sheen.
The 35-year-old opted to take voluntary redundancy from ITV Studios last year after the broadcaster decided to axe The South Bank Show.
In his new role at Channel 4, Cain will be responsible for taking a strategic view of the broadcaster's cultural output as part of an arts board established by Tabitha Jackson, Channel 4's new arts commissioner.
Speaking to The Guardian, Cain said: "I used to get very impatient and bored with long-form television, all the hours of talking.
"I am looking forward to fast turnarounds. I have never been interested in a reverential, worthy approach to the arts."
Last September, the BBC hired former Tate director Will Gompertz as its first ever arts editor, with a mission to increase arts coverage across the corporation's output.