This will be her second time speaking to the Democratic National Convention.
But the stakes are higher than ever before as Ms Harris tries to unite the party behind its presidential candidate, Joe Biden, while also introducing herself to a national audience who may be tuning into the campaign for the first time.
“For somebody with her wealth of background and experience, she’s still fresh. She’s still new,” said Ohio Democratic Representative Marcia Fudge, a former chairwoman of the Congressional Black Caucus who endorsed Ms Harris’ own 2020 presidential primary run before formally throwing her support behind Mr Biden in March.
“I think people are looking for that.”
The daughter of Jamaican and Indian immigrants, Ms Harris has shined in key moments before.
She was lauded for drawing a crowd of 20,000 to the announcement of the start of her presidential campaign in Oakland last year.
Her subsequent tough questioning of two Trump nominees, Brett Kavanaugh for Supreme Court justice and Bill Barr for attorney general, during Senate confirmation proceedings was a similar high point, as was her broadsiding Mr Biden during a debate over his opposition to busing in the 1970s to integrate public schools.
Heading to the Badger State where President @realDonaldTrump has been putting American workers first since DAY ONE! pic.twitter.com/IYPdxuJZ8F
— Mike Pence (@Mike_Pence) August 19, 2020
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“I hope that they see themselves in her when they hear her speak,” Mari Urbina, national director of Indivisible, a progressive advocacy group, said of young first- and second-generation immigrants across the country.
“And that they are motivated to understand that, not only do they have to be part of getting us out of this nightmare, but that they also can feel part of this historic change that we’re all about to embark on.”
But Ms Harris also launched her presidential bid with expectations that she would electrify the field, only to see her campaign struggle to find a consistent message and fizzle, with the California senator dropping out months before the first votes were cast.
She also will not have the spotlight all to herself on Wednesday: the man she is vying to unseat, Vice President Mike Pence, is visiting battleground Wisconsin in the hours before Ms Harris’ speech.
Convention addresses are often the most important for those selected as vice presidential candidates, but also only the start of a far bigger role in public political consciousness should their ticket win.
There is potentially even deeper repercussions for Ms Harris, though, since she could be called upon to step into the role of party standard bearer as soon as 2024, should Mr Biden, who will be nearly 82 by then, opt not to seek a second term.
Mr Biden has not expressly said he’d serve just a single term, but he has talked openly about being a bridge to a new generation, setting up Ms Harris as a natural successor.
Adrianne Shropshire, executive director of BlackPac, which works to mobilise African American voters nationally, said Ms Harris will necessarily stay focused on defeating Mr Trump in November, not future presidential races.
But she said her speech will likely carry special significance for women around the country that could resonate for years.
“The historic nature of this, I don’t think can be overstated,” Ms Shropshire said.
“It will be a really profound moment for women.”
The campaign is also deeply personal for Ms Harris.
During her first appearance with Mr Biden last week, she spoke of her friendship with the former vice president’s son Beau, who died of brain cancer in 2015.
He and Ms Harris had became close while both were state attorneys general.
“He really was the best of us.
“And I would ask him, ‘Where’d you get that, where’d this come from?’ He’d always talk about his dad,” said Ms Harris, her voice thick with emotion, during her first joint appearance with Mr Biden last week at a high school gymnasium near his home in Delaware.
The former vice president said that relationship had made Ms Harris ”an honorary Biden for quite some time”.
