The comics creator stated that a movie based on the character, to be released in 2011, could feature the actor.
He told Moviefone: "I would love us to do something with Will Smith. It would be a real leap to make Captain America black... then again, I don't know."
Lee added that such a casting may be down to who makes it to the White House in November, as a Barack Obama victory could affect Hollywood.
"It might be a really smart thing. If Barack Obama becomes President who knows... suddenly a lot of our characters will be black," he said.
Earlier this year, it was reported that Leonardo DiCaprio was the top choice among Marvel executives to play Captain America.