"Ma'am, I need to sit somewhere else. We used to be married," Roberts' character explains to a flight attendant upon discovering her seatmate is her ex-husband.
"Worst 19 years of my life," Clooney's character says.
"We were only married for five," she shoots back.
"I'm counting the recovery," he deadpans.
Believing their daughter getting married would be the same mistake they once made, the former couple teams up together to end the soon-to-be newlyweds' relationship.
In 2001, Roberts and Clooney first appeared together in "Ocean's Eleven" as estranged couple Danny and Tess Ocean and reprised their roles in 2004's "Ocean's Twelve." They've also acted together in "Confessions of a Dangerous Mind" (2002) and "Money Monster" (2016).
Roberts recently spoke with USA TODAY about the power of acting alongside a familiar co-star: Working on Starz's Watergate drama "Gaslit" with her longtime friend Sean Penn helped streamline the process of conveying their characters' relationship on-screen, she said, unlike actors who've only recently met.
"All the time and energy that you spend getting to know people, getting to understand people, trying to make people comfortable with you, trying to get people to understand where you're coming from, or how you work, or what you need from them, that's weeks and weeks of work that doesn't exist," Roberts added.
Read the full USA TODAY interview: Julia Roberts explains why she wanted Sean Penn as her TV husband in Watergate series 'Gaslit'
Now, the actress, known as the leading lady in several classic romantic comedies throughout the '90s including "Pretty Woman," "My Best Friend's Wedding," "Mystic Pizza" and "Notting Hill," makes her return to the rom-com genre after more than 20 years. Roberts previously spoke about why she's shied away from rom-com projects for so long.
'A lot has changed': Julia Roberts doesn't think 'Pretty Woman' would be made today
"What I’ve learned is that you always want to do what you’re not doing," Roberts said in an April interview with The New York Times Magazine. "Whenever I’m in a comedy, I think I just want to be at a table with a cup of tea sobbing over something. Then you’re doing that, and you think, 'Oh to be wearing a pretty dress and laughing.' "
She added: "People sometimes misconstrue the amount of time that’s gone by that I haven’t done a romantic comedy as my not wanting to do one. If I had read something that I thought was that 'Notting Hill' level of writing or 'My Best Friend’s Wedding' level of madcap fun, I would do it."
Contributing: Erin Jensen
This article originally appeared on USA TODAY: Julia Roberts, George Clooney new movie: 'Ticket to Paradise' trailer