The remarks "were not about Hillary Clinton," Obama told The Associated Press as he left a campaign rally.
His wife, Michelle, made the statement during a speech last week in which she talked about how she and her husband balanced the demands of raising children with campaigning.
Some political commentators have interpreted her words as a veiled attack on his chief rival for the Democratic nomination.
Obama said his wife's comment was taken out of context.
"She has been making that speech constantly about the decision we made to make sure that our family was strong," Obama said, "because if our family wasn't that strong then we couldn't be a strong leader in the White House."
"The whole thing about Hillary has been completely fabricated," Obama added. "You guys have got to get it off your minds."
Later in the day, Obama attended a Brooklyn rally, where he recalled living in the Park Slope neighborhood of the borough while a student at Columbia University.