Once a rival for the top job, the California senator of Indian-Jamaican heritage had long been considered the front-runner for the number two slot.
Mr Biden will face President Donald Trump in the election on 3 November.
At a White House news conference on Tuesday, President Trump, a Republican, described Ms Harris as his number one draft pick.
Ms Harris will debate president Trump’s running mate, Vice-President Mike Pence, on 7 October in Salt Lake City, Utah.
Only two other women have been nominated as vice-presidential candidates for a major party – Sarah Palin by the Republican Party in 2008 and Geraldine Ferraro by the Democrats in 1984.
Neither ended up on the winning ticket.
A woman of colour has never been appointed to a presidential ticket by either of the two main American political parties.
No woman has won the US presidency either.
Ms Harris later tweeted that Mr Biden “can unify the American people because he’s spent his life fighting for us.
And as president, he’ll build an America that lives up to our ideals.
She repeatedly clashed with Mr Biden during the primary election debates, most notably criticising his praise for the “civil” working relationship he had with former senators who favoured racial segregation.
The Democrat was born in Oakland, California, to two immigrant parents, an Indian-born mother and Jamaican-born father.
She went on to attend Howard University, one of the nation’s preeminent historically black colleges and universities. She has described her time there as among the most formative experiences of her life.
Ms Harris says she’s always been comfortable with her identity and simply describes herself as “an American”.