George Clooney, who received the Golden Lion for Lifetime Achievement from his “Jay Kelly” co-star Laura Dern on opening night of the Venice Film Festival, sat down for a masterclass at the Lido’s Match Point Arena to look back on a career spanning nearly five decades.

His relationship with Venice stretches back nearly three decades, beginning with “Out of Sight” and continuing with films including “Good Night, and Good Luck,” “Michael Clayton,” “Gravity,” “Suburbicon,” “Wolfs,” and, last year, Noah Baumbach’s “Jay Kelly.”

During the wide-ranging talk, Clooney reminisced about the risks he took to make “Good Night, and Good Luck” two decades ago, recalling that he “mortgaged my house to make it” before bringing the film to Venice in 2005, where he watched it with an audience for the first time.

The story — about legendary CBS journalist Edward R. Murrow standing up to Sen. Joseph McCarthy at the height of the Red Scare — remained deeply personal to Clooney, whose father, Nick Clooney, was a journalist and news anchor.

He said he felt compelled to revisit the film the stage at a moment when its themes of press freedom, political intimidation and the responsibility of journalists to challenge those in power still strike a chord.

“When we decided to do the play and put the play back on, it felt like those words were more urgent than ever at a time when the networks were caving and law firms were caving and universities were caving to the whims of, you know, a populist. And so I thought it was important to say those words,” he said about the Broadway adaptation. He paid tribute to his father for inspiring his activism and the launch of the Clooney Foundation, which he said has already “gotten 100 journalists out of jail.”

 “When I was a kid, I was like seven or eight, believe it or not, my dad used to say to me, ‘I don’t give a shit what you do in life. I don’t care. You have one responsibility, and that is to challenge people with more power than you and to defend people with less power than you. That’s it.’”

Clooney said the philosophy continues to shape both his activism and that of his wife, human rights lawyer Amal Clooney.

“My wife and I spend a good portion of our lives trying to follow those same rules,” he said, pointing to people “born in a war zone,” suffering from hunger, women who are mistreated and imprisoned journalists. “Those people need some luck. And so our job is to be part of that solution.”

Clooney also recalled his own years of campaigning to bring attention to atrocities in Darfur and admitted he hasn’t been as successful as his wife in actually bringing perpetrators to justice.

“I had success at making it loud, but not a lot of success at making it stop, or certainly not a lot of success at bringing people to justice,” he said. “And then 20 years later, my wife finally puts some of these guys on trial and gets them thrown in jail … She got it done,” he added, calling Amal “a badass.”

Clooney also recalled watching Amal take on the case of Nadia Murad, the Yazidi survivor of ISIS atrocities who later won the Nobel Peace Prize. When Murad first came to their home, Clooney said Amal — already overwhelmed with cases — had warned him not to let her take on another one.

Four hours later, he found the two women sitting on the floor crying together. “I said, ‘You’re taking the case,’” Clooney recalled.

During the panel Clooney passionately also discussed the balance of power between an actor and his director.

“The director is the painter and everything else is the paint,” he said. “That actor is the paint. The music is the paint. The sound design, the cinematography. Those are all paints. And the director gets to dip his brush into each one of those,” he added.

“You know, an actor only affects it as much as the director decides,” Clooney continued. “I could change any actor’s performance as a director. I could cut them out, for that matter.”

Clooney talked about working with Terrence Malick on “A Thin Red Line.” Malick “hadn’t worked in fifteen years and wanted to come back and do a film,” he said. “So I thought I’m going to help him get this film made, and I’m going to do this part.” Clooney traveled to Australia and shot “A Thin Red Line” for months, “and then he [Malick] cut me completely out, except the last scene in the film, the very last scene.”

“And I watched it. I was like: he cut me completely out. You’ll leave me in the last scene. My God, I look like an asshole.”

He also told the room packed with aspiring actors and filmmakers that success in Hollywood depends partly on luck — but that they can also manufacture some of their own. “You have to end up being the right person in the right place at the right time,” he said. “You can create a lot of that luck.”

He pointed to his own career-making role as pediatrician Doug Ross on “ER,” noting that he had already appeared in seven television series before landing the NBC medical drama.

“There is just a moment where something works. But you gotta keep chasing it,” Clooney said. “You gotta be out there and available and go, you know, ‘I’m your guy.’”

Then, almost as if to prove his point, a 25-year-old recent film school graduate from Belgium, originally from Algeria, stood up during the Q&A and asked Clooney for a job on one of his productions. She said she hoped to become a director but wanted to gain experience in the industry first. Clooney began quizzing her about what she wanted to do and offered to come work on one of his upcoming projects that will shoot in Italy.

Clooney also struck a philosophical note as he remembered, with visible emotion, the death of his sister from cancer last year and how being with her in her final moments.

“She died very quickly, and I was with her when she died. And there was this feeling, being with her, holding her hand when she died, understanding how brief all of this is. It was minutes ago that she and I were little kids together; Minutes ago we were holding hands as little kids,” he said.

“Time goes fast. All of this. And so we have to find nothing but joy,” he continued.