"Bo is wonderful. He is the smartest dog on the planet. He is my son. I have two girls and a boy," the first lady joked.
Bo, a Portuguese Water Dog, has gotten a lot of media attention since the Obamas got him as a gift from the late Sen. Edward Kennedy (D-Mass.) in 2009.
He has starred in White House videos, greeted tourists and served as the inspiration behind last year's Christmas decorations at 1600 Pennsylvania Ave.
The famous pooch even had a cameo on NBC's "Late Night With Jimmy Fallon" last month.
"He has a very busy schedule. I mean appearances. I'm thinking about getting him an agent," Obama said.
The first lady came to Bo's defense when Letterman suggested that his particular breed may be a "little loopy."
"No, they're not," she quickly interjected. "He's a very sweet dog. I'm not being biased. He is really a good dog."
Obama told Letterman that the well-loved canine has a special way of letting her know when he has to do his doggy business.
"He will come up and he'll put his paw on your leg and he kind of nudges you and then you're like, 'What do you want?' and then he gets excited and you say, 'You want to go out?' and then he starts barking," she said.
"Is this what Biden does?" asked Letterman, eliciting laughter from Obama and the audience.
Obama was appearing on the late-night show to promote Joining Forces, an initiative she started with Jill Biden to support members of the military, veterans and their families.
"Many of us don't understand the challenges and the struggles. We take it for granted, because we have 1 percent of this nation serving and protecting the rights of the other 99 percent of us," she said.
Obama said that as someone who didn't come from a military family, it wasn't until she began campaigning and traveling to military bases that she realized that most Americans have "no clue" about the level of sacrifice being made.
"This campaign is designed to make sure that every single member of our armed forces, our veterans and their families understands that they live in a grateful nation," she said.