Opening the museum in Washington, President Barack Obama pointed out the highs and lows of being black in America, from slavery and segregation to voting rights and economic leaders.
That mixtures is still present in America today, Mr Obama said, with successes such as his presidency, and trials such as the police killings of black men.
"We are not a burden on America. Or a stain on America... we are America. And that's what this museum explains," Mr Obama said.
He and first lady Michelle Obama joined Ruth Bonner, a 99-year-old direct descendent of a slave, and her family as they rang a bell from the First Baptist Church of Williamsburg, Virginia, to signal the museum was officially open.
The church, believed to be among the first Baptist churches organised entirely by black people, acquired its Freedom Bell in 1886. It will return to the church for its 240th anniversary later this year.
Civil rights veteran John Lewis, a Democratic congressman from Georgia who co-sponsored the bill that created the museum, said he hopes visitors will come away with a healthy respect for human dignity, "and a stronger commitment to the idea of justice, truth and democracy".
"This place is more than a building, it is a dream come true," Mr Lewis said.