The 50-year-old "Fury" star was taunted by the "Hangover" franchise's funny man in the palpably awkward interview, which not-so-mildly kicked off with questions about naked pictures in Playgirl magazine, Pitt not showering and looking "like [Adolf] Hitler's dream."
Not to worry, Pitt eventually got his revenge.
Incidentally, the star did few TV interviews as he promoted his World War II tank film, which opened last week. Instead, the actor did several print interviews and fielded questions on the red carpet at the film's Washington, D.C. premiere, so it's surprising that he took part in the less-controlled setting, which previously took aim at President Barack Obama, Justin Bieber, Bradley Cooper and several others.
The irreverent host, who didn't even bother with Pitt's real name, called him "Bradley Pitts" or "Bart Pit" and described his latest flick as "Furry."
An increasingly agitated Pitt went along and took what the "Birdman" star dished up.
At one point, the host presented Pitt with a festively wrapped "bassoon," which suspiciously resembled a bong.
"Thank you. You know I'm a dad now," Pitt replied after accepting the gift. "We don't bassoon at my house anymore."
Then going "off topic just a bit," Galifianakis asked Pitt whether he could borrow "one or two" of the father of six's "sperm."
"No, I think that would be inappropriate," Pitt said.
Upon being asked about his charity work, Pitt tried to promote the Make It Right Foundation only to have Galifianakis hit a buzzer and welcome comedian Louis C.K. to deliver a totally unrelated stand-up bit.
More clobbering came after that with the host delivering this one liner: "Is it hard for you to maintain a suntan?" he asked, "because you live in your wife's shadow."
Of course, Galifianakis was referring to Angelina Jolie, whose long-awaited union to the actor finally came over the summer. The Oscar-winning actress and mother of their children was recently named an honorary dame by Queen Elizabeth II and is directing "Unbroken," a competing World War II film.
Pitt just looked around the sparse set and didn't answer, obsessing over the fact that he lost his last piece of gum, which he chomped on for the duration of the interview.
Galifianakis also didn't let Pitt traipse by without taking a sideways jab at his ex-wife Jennifer Aniston.
"Tell me what it was like the first time that you laid eyes on Angelina. Was it like one of those classical love stories like when Ross first saw Rachel. You know, that show 'Friends,' have you seen that?" he asked.
Not only did Pitt know the show, but he appeared on his then-wife's comedy as her spurned lover back in 2001.
Galifianakis proceeded to play the "Friends" theme song to make the awkward situation even worse.
"I like that song," Pitt said.
Then Galifianakis dealt the final blow, asking Pitt whether he thought people focused "too much on his looks and they don't even realize that you're just a [expletive] actor."
And that's when Pitt spit his gum right into Galifianakis' eye.
It was only a matter of time. Follow me on Twitter @NardineSaad.