Clarke and Harington, who play Daenerys Targaryen and Jon Snow on the HBO series, discussed their friendship and on-screen romance in the summer issue of Vanity Fair.
"I'll tell him, 'Kit, stop being a [expletive] -- stop being so grumpy.' Like I would with my brother," Clarke said of their dynamic.
Harington is engaged to former Game of Thrones star Rose Leslie, who is close friends with Clarke.
"If you've known someone for six years, and they're best friends with your girlfriend, and you're best friends with them, there is something unnatural and strange about doing a love scene," the actor said of filming with Clarke.
"We'll end up kissing and then we're just [expletive] ourselves with laughter because it's so ridiculous," he added.
Game of Thrones Season 7 ended with Daenerys and Jon having sex, unaware Jon is the son of Daenerys' late brother Rhaegar Targaryen. Jon's true parentage makes him a rival to Daenerys' claim to the throne.
"I've worked so hard, I don't want to share that throne," Clarke said in an interview with Entertainment Weekly after the finale. "The throne's big enough for one dragon bum, and that's mine. That's it!"
"I said to Emilia it's going to be a really cool scene when they find out [they're related]," Harington added. "It could be them walking off into the sunset. It could be them killing each other."
Game of Thrones will return for an eighth and final season in 2019.