The two-time Oscar winner was cutting tabacco in Kentucky when a cousin came to stay and asked him if he would like to play a role in a movie about horse racing (the 1982 film And They’re Off).
Clooney said yes, and the rest is, as they say, is history.
Characteristically modest, the 58-year-old insists the only reason he didn’t follow in his journalist father’s footsteps was lack of skill.
Looking at his CV, that’s hard to believe.
Clooney attained worldwide fame in the 1990s for his role as Dr Doug Ross in ER, for which he won an Emmy.
He then went on to make the rarely seen transition from a TV actor to a film star.
Clooney tells Sky News it’s a hierarchy he can’t get his head around.
“Actors have a pecking order that’s crazy. Film actors look down on television actors who look down on commercial actors, and then theatre actors look down on the film actors.
“Even in LA you’ll have guys who’ve lived there for 30 years who are from New York, but they’re like, ‘I’m really a New York actor’.”
I tell him it’s a little like a well-known Monty Python sketch on class, and he readily agrees.
But for Clooney, it’s the nature of the work rather than its genre that matters. And now, after nearly 20 years away, he’s back on the small screen.
“I’ve been working in television for years, producing, directing or writing television. But I guess I haven’t been on camera in a while.
“I didn’t think of it as coming back to TV, I just thought of it as a place where we could tell a story.
“I didn’t really care about the medium, I just like to work.”
And work he has, juggling his TV and film career with an active role as a political and economic activist.
Of course, it’s impossible to note Clooney’s activism without mentioning his wife, human rights lawyer Amal Clooney.
The pair married in 2015, becoming parents to twins Alexander and Ella three years later.
So, did Clooney see himself settling down as a family man in his late 50s? Apparently not.
“I just go in the direction my life and the world is taking me.
“I didn’t expect to have children and a wife at this point in my life and then Amal walked in. So everything changed for me in a considerably beautiful and unexpected way.
“I’ve always been a hard worker and believed in that. I have plenty of things I wish I’d done differently, but if it all ends up here, then I suppose it was necessary.”
Today, aside from chatting about his inauspicious career beginnings, and clear adoration of his wife and children, Clooney is promoting his new TV miniseries Catch-22.
He produced, directed and stars in the show.
Based on the 1961 Joseph Heller novel, the six-parter tells the story of Captain John Yossarian (Yo-Yo) a US Army Air Forces B-25 bombardier in World War II.
While the lead role is played by 33-year-old Girls star Christopher Abbott, Clooney plays the parade-obsessed Lieutenant Scheisskopf.
A previously outspoken critic of Donald Trump, Clooney makes no bones about the parallels with today’s turbulent political times.
“We have a 74-year-old president who wishes we were still in the 1950s, which was good if you were a white guy.
“Part of the idea of a Catch-22 is that old white men are making decisions that young people are going to die for. And I think that that is something that we should argue about endlessly…
“And part of the reason you feel these waves of populism coming up is because there’s huge swaths of people that feel like they are fighting against a system that they can’t possibly win.”
Clooney, who grew up in the ’60s and ’70s at the time of anti-Vietnam war protests, believes that “as a citizen, it’s your right and oftentimes your responsibility to question your government”.
Especially, he says, when the people sent to the frontline are “18-year-old kids who don’t question authority”.
He thinks those who are older, with more experience – like Yo-Yo in Catch-22 – are likely to have more to say about it.
He says if you’re 30, and being sent over the top with just a bayonet, you’re likely to be questioning your motivation to fight, especially when “there’ll be a McDonald’s here in 10 years whoever wins”.
So why make the show now, nearly 60 years after the novel was published?
Clooney thinks these “insane” and “absurd” times are perfect to resurface the political satire to remind us “these things are temporary and are cyclical”.
He chose TV rather than film as he felt the story needed six hour-long episodes “just to go through all the characters”.
And even for those who haven’t read the 450-page novel, the title will be instantly recognisable, having passed into everyday speech.
But it could have been very different, as Clooney explains the novel was very nearly called something else.
“It was originally Catch-18 and then Uris wrote a book that had 18 in it (Leon Uris’s Mila 18). Then he tried to make it Catch-11 and Ocean’s Eleven came out.
“He wanted to make it Catch-17 but the film Stalag 17 was released. It was like he kept going through it until he came on Catch-22.”
A little like Clooney becoming a Hollywood star, husband and father – some things, it seems, are just meant to be.
:: Catch-22 begins on Thursday 20 June at 9pm on Channel 4