Biden announced the decision in an email to supporters.
"I know a thing or two about being Vice President. More than anything, I know it can't be a political decision. It has to be a governing decision. If the people of this nation entrust me and Kamala with the office of President and Vice President for the next four years, we're going to inherit a nation in crisis, a nation divided, and a world in disarray. We won't have a minute to waste. That's what led me to Kamala Harris," Biden said in the email.
He also harkened back to the first time he met Harris through his late son, Beau.
"They were both Attorneys General at the same time. He had enormous respect for her and her work. I thought a lot about that as I made this decision. There is no one's opinion I valued more than Beau's and I'm proud to have Kamala standing with me on this campaign," he said.
In a tweet, Harris said she's honored to join Biden and will "do what it takes to make him our Commander-in-Chief."
Soon after the announcement, the Biden campaign sent out a fact sheet to supporters titled "Ready to Lead" about Harris' qualifications and announced that the pair would deliver remarks in Wilmington, Delaware, on Wednesday.
Next week, the Democrats hold their national convention -- largely a virtual affair because of the ongoing coronavirus pandemic -- with former first lady Michelle Obama, former second lady Jill Biden, former President Barack Obama and the former vice president headlining each of the four nights.
Harris was already slated to speak at next week's Democratic National Convention in a primetime slot on Thursday. Now that's she Biden's pick for vice president, she'll deliver a speech Wednesday, just before Obama is set to close out the night.
In 2019, when Harris was a presidential candidate, she gave this advice for young women:
History is made
As the vice presidential search wore on against the backdrop of racial tensions and social change, Biden was frequently questioned about whether he would choose a woman of color as his running mate.
By choosing Harris, who is Black and Indian American, Democrats are sending a powerful and historic statement ahead of the November election as the nation continues to grapple with social change. If elected, Harris would not only be the first woman to serve as vice president, but would also be the first person of color to be second in command and the highest-elected Asian American in history.
The junior senator from California has already achieved a number of historic milestones as the second Black woman and first South Asian American senator in history. She was also the first person of color and first woman to serve as California's attorney general. Her friendship with a fellow attorney general, the late-Beau Biden, remains a bond between Harris and the Bidens.
Reaction from the political world
Responses the announcement were swift.
Jill Biden tweeted at Harris' husband, Doug Emhoff, who has the potential to become the first second husband in American history.
"Are you ready?" she tweeted, to which he responded, "Ready to work!"
Susan Rice, former national security adviser to Obama who was also near the top of Biden's shortlist for vice president, was quick to issue a statement congratulating Harris.
"Senator Harris is a tenacious and trailblazing leader who will make a great partner on the campaign trail," she said. "I look forward to supporting the Biden-Harris ticket with all my energy and commitment."
Obama called it "a good day for our country" in a tweet about the announcement.
"I've known Senator @KamalaHarris for a long time," he wrote. "She is more than prepared for the job. She's spent her career defending our Constitution and fighting for folks who need a fair shake."
House Speaker Nancy Pelosi, in a statement, called the choice of Harris a "historic and proud milestone for our country."
Both former president Bill Clinton and Democratic nominee for president in 2016 Hillary Clinton tweeted at Biden and Harris welcoming the decision.
Hillary Clinton said Harris has "already proven to be an incredible public servant and leader," an argument the now Biden-Harris campaign is already touting.
Michigan Gov. Gretchen Whitmer -- who recently met with Biden, a source confirmed to ABC News -- used "#WeHaveHerBack" in her tweet congratulating Harris.
Florida Rep. Val Demings, another member of Congress who made Biden's shortlist, expressed gratitude for being considered and excitement to help the presumptive Democratic ticket win in November.
"For a little girl who grew up poor, Black and female in the South to be considered during this process has been an incredible honor. I feel so blessed. To see a Black woman nominated for the first time reaffirms my faith that in America, there is a place for every person to succeed no matter who they are or where they come from," Demings said in a statement.
Sen. Bernie Sanders, the last to suspend his 2020 presidential campaign amid the coronavirus pandemic, offered his congratulations in a tweet.
"Congratulations to @KamalaHarris, who will make history as our next Vice President," the senator from Vermont wrote. "She understands what it takes to stand up for working people, fight for health care for all, and take down the most corrupt administration in history. Let's get to work and win."
Another former presidential candidate who was also on the vice presidential shortlist, Sen. Elizabeth Warren, D-Mass., added in her congratulatory tweet that she is "so looking forward to seeing Kamala take on Pence on the debate stage."
Former Alaska Gov. Sarah Palin, the second woman to have been nominated by a major political party for vice president, celebrated the historic nature of Harris joining Biden on the ticket in an Instagram post that also referred to Geraldine Ferraro, who was former Vice President Walter Mondale's Democratic running mate in 1984.
"Climb upon Geraldine Ferraro's and my shoulders, and from the most amazing view in your life consider lessons we learned," Sen. John McCain's former Republican running mate wrote, adding six tips for Harris heading into the election.
Palin's tips included to trust no one out of the chute, to connect with media and voters in a personal way, to remember the women who paved the way and to have fun.
Both the Trump and Biden campaigns worked quickly to fundraise off the news.
President Donald Trump tweeted out a video slamming Harris in response to the news and the campaign texted supporters: "Biden picks Phony Kamala for VP! He isn't smart enough to see her lies."
Biden's campaign website immediately posted Biden-Harris swag for sale and the campaign's deputy digital director Clarke Humphrey said on Twitter the campaign broke its best fundraising hour ever following the announcement.
Vice President Mike Pence offered his first reaction to the news while at a campaign event in Mesa, Arizona.
"Let me take this opportunity to welcome her to the race," Pence said to laughter. "I mean, we all know -- look. Joe Biden and the Democratic Party have been overtaken by the radical left, so given their promises of higher taxes, open borders, socialized medicine and abortion on demand. It's no surprise that he chose Sen. Harris to be his running mate."
Pence also teased the first the vice presidential debate on Oct. 7 in Utah.
"So my message to the Democratic candidate for vice president: Congratulations," he said.
Later, during a press conference at the White House, Trump was asked about Harris.
"I was a little surprised at the pick. A lot of people would say that might be the pick," the president said.
"We'll see how she works out," Trump added. "She did very, very poorly in the primaries, as you know. She was expected to do well, and she was -- she ended up at right around 2%. And spent a lot of money."
He went on to say he wouldn't forget how "nasty" she was to Brett Kavanaugh during his Supreme Court nomination -- and suggested Biden should feel disrespected by Harris too.
"It is hard to pick somebody that is disrespectful. She said things during the debate, during the Democratic primary debates, that were horrible about Sleepy Joe. And I would think that he would not have picked her," Trump said.
In the Senate, Harris serves on the Homeland Security and Governmental Affairs Committee, the Select Committee on Intelligence, the Committee on the Judiciary and the Committee on the Budget. And her tough questioning of Kavanaugh was one of the instances that increased Harris' popularity among Democrats on a national level.
In recent months, Harris advocated for legislative policies aiming to alleviate the aftershocks millions of Americans felt in the wake of the novel coronavirus. She also drew on her experiences as a woman of color to call for change in the aftermath of George Floyd's death. Recently, Harris, along with her colleague and former presidential campaign trail rival, Sen. Cory Booker, gave emotional arguments in favor of making lynching a federal crime. The pair, along with other high-profile Democrats, also introduced legislation to make Juneteenth a national holiday.
During the Democratic primary campaign, Harris -- the sole Black woman in the running -- was amplified as a top contender following a debate performance in which she took Biden to task over his past stances on busing policies.
"There was a little girl in California who was part of the second class to integrate her public schools and she was bused to school every day. That little girl was me," Harris said at the time.
Following the debate, Biden complimented Harris.
"She is a first-rate intellect, a first-rate candidate and a real competitor," he told reporters at an event in Iowa last year. "I have mixed emotions about it because she is really a solid, solid person and loaded with talent. I'm sure she's not dropping out on wanting to make the changes she cares about."
Harris suspended her presidential campaign in early December, and endorsed Biden after his Super Tuesday sweep.
She served as a top surrogate for the Biden campaign amid the pandemic landscape and was one of his top fundraisers. With traditional campaign events severely limited due to safety concerns, Harris participated in a variety of virtual events to back Biden, including roundtable discussions, state-specific appearances and even a virtual concert fundraiser featuring high-profile DJs.
Harris' entry to the presidential campaign is likely to see criticism from some social activists who do not feel that she could serve as an agent of change for policing reform given her past record as a prosecutor, a notion Harris adamantly pushes back against.
"This is simply wrong, it's just absolutely wrong. When I was attorney general of California, I instituted one of the first requirements that law enforcement officers receive training on racial implied bias and procedural justice," Harris said during a cable news interview in June.
"I'm the first that created a whole division and approach, that actually became a national model," she added.
ABC News' Kendall Karson, Justin Gomez, Will Steakin, Johnny Verhovek, Katherine Faulders, Soo Rin Kim, Averi Harper and Michelle Stoddart contributed to this report.
This report was featured in the Wednesday, Aug. 12, 2020, episode of “Start Here,” ABC News’ daily news podcast.
"Start Here" offers a straightforward look at the day's top stories in 20 minutes. Listen for free every weekday on Apple Podcasts, Google Podcasts, Spotify, the ABC News app or wherever you get your podcasts.