He then proceeded to push a button which started playing the theme song from Jennifer's hit sitcom.
Taking it on the chin, Brad mumbled: "I like that song."
It came just after the World War Z star was asked if it's hard for him "to maintain a suntan".
When Pitt asked why, Galifianakis zinged: "Because you live in your wife's shadow," and then claimed he "had the same thing with [Condoleezza] Rice".
The skit started off with the host complaining that he was lowering his standards by interviewing "Bradley Pitts" after President Barack Obama appeared on the show.
"I'm just saying I interviewed the President last time and now I have to go back to interviewing dumb actors," Galifianakis told someone off camera as Pitt stared ahead, bored.
The first question for the 50-year-old was: "How old were you when you lost your virginity? Zero?"
When Brad didn't answer, Galifianakis offered to tell his own story, and the Fight Club star said he "would really not like to hear that".
He is widely considered one of Hollywood's biggest heartthrobs, so Galifianakis had no problem mocking Brad's looks.
"You play a lot of people who are Nazi haters which is weird to me because you look like Hitler's dream," the host teased, before asking if he could borrow "one or two sperms".
He then got Pitt's gum - which the pair swapped during the interview - spat in his eye when he asked the final question: "Do you think people maybe focus too much on your looks and don't even realise that you're just a s****y actor?"
At one point, Pitt began talking about his charity work, and Galifianakis' response was to get Louis CK to come out and tell jokes to "liven things up".
The father-of-six did walk away with a present, however, in the form of a huge bong which Galifianakis insisted was just a bassoon.
"I thought it was a bowling ball," Brad joked. "You know I'm a dad now, we don't bassoon in my house anymore."
The increasingly awkward interview also included Galifianakis mentioning seeing Pitt naked in Playgirl magazine and asking, out of the blue: "When you and Clooney get dressed up in your tuxes together do you ever kind of look at each other and go: 'Aren't we a couple of dapper Dans?'"
Sadly, Pitt said that "never happened".
The star was there to plug his new film Fury, and as usual Galifianakis wasn't being of much help when he referred to it as "Furry" and then just asked when it "comes out on DVD".
- Daily Mail