Grilled by host Bret Baier, Harris also defended President Joe Biden's mental fitness, her years as his vice president and her previous support of gender-affirming surgery for transgender inmates.
Harris and Baier frequently talked over each other, and Harris grew visibly frustrated, but she delivered her message for the US election to a conservative audience that might not often hear it.
She was asked to defend the administration's early decision to reverse some of the restrictive border policies of Republican rival Donald Trump when he was president and to respond to a mother who testified in Congress about the loss of her daughter at the hands of an immigrant in the US illegally.
"I'm so sorry for her loss, but let's talk about what is happening right now," Harris said.
She said Trump told Republicans to reject a bipartisan immigration bill early this year because "he preferred to run on a problem instead of fixing a problem."
Trump and Republicans have claimed that immigrants are fuelling violent crime in the United States, although studies show immigrants commit crimes at lower rates than others.
Asked about her recent comment that there was "not a thing" she would change about the actions of the Biden administration, Harris said: "Let me be very clear, my presidency will not be a continuation of Joe Biden's presidency."
She said she would bring in new ideas from Republicans and business leaders to solve housing shortages and expand small businesses.
Harris was a vocal supporter of Biden when he faced mounting questions about his mental fitness after a disastrous June debate with Trump before dropping out of the race in July. She was asked to defend those statements.
Biden has the "judgment" and "experience" to be president, she said, while questioning Trump's fitness for office.
She was pressed on her position on using taxpayer funds for gender-affirming surgery for transgender inmates, including those who are undocumented. Trump has spent millions of dollars in ads on the subject in battleground states.
"I will follow the law," Harris said, noting that the US Bureau of Prisons provided gender-affirming treatments under Trump. She accused him of "throwing stones when you live in a glass house."
The nearly 30-minute interview marked the first time Harris has appeared as a presidential candidate on the conservative media network, which often features opinion show hosts who mock her and other Democrats and tout Trump's policies.
Within minutes of the interview's end, the Trump campaign released a statement calling it a "train wreck."
David Urban, a political strategist and past Trump campaign aide, said Harris gave an uneven and subpar performance, avoiding responsibility and making Trump the scapegoat.
Democrats said Harris went on unfriendly territory and made it through without any gaffes.
