Rice's sworn testimony could also have significant implications for President Bush's re-election campaign, which relies to a great extent on his national security credentials.
It may also determine whether the official history of Sept. 11 will be widely accepted or the victim of partisan interpretation.
Her appearance will be televised nationally by CBS News, and webcast live on CBSNews.com, beginning at around 9 a.m. ET.
Rice met earlier for four hours with the commission, and her public testimony was assured only after Mr. Bush relented under public and political pressure.
Appearing on morning television news shows Thursday in advance of the hearing, commission co-chairmen Thomas Kean and Lee Hamilton promised vigorous questioning but also pledged to be fair.
"We're going to give some very searching difficult questions for Dr. Rice," Hamilton, a former Democratic congressman from Indiana, said on the CBS News Early Show.
"We're not playing a game of gotcha here with any of our witnesses," he added.
"I think the big job for us is not to exercise 20/20 hindsight," Hamilton said. "I think we have to put ourselves in the position of the policy-makers at the time and the environment in which they worked."
Bush administration officials said Rice wanted to detail the administration's anti-terror actions before the attacks and show that terrorism was a priority, without offering a blow-by-blow rebuttal to former counterterror adviser Richard Clarke.
Clarke, who resigned from the administration a little over a year ago and has written a book about his experiences there and in the Clinton administration, has claimed that Bush officials, and Rice in particular, did not consider al Qaeda an urgent priority before the attacks.
"This is the 9-11 commission, not the Dick Clarke commission," said Sean McCormack, a spokesman for the White House National Security Council.
White House aides have said that Rice will mount a strong defense of the Bush administration's approach to terror in the months before the Sept. 11 attacks.
Mr. Bush said Monday that Rice "knows exactly what took place and will lay out the facts" when she testifies before the Sept. 11 commission.
Rice is to begin her testimony with a 20-minute statement outlining the administration's position.
Rice was not expected to offer an apology to Sept. 11 victims, as Clarke did during his testimony two weeks ago. She was prepared to "speak about our sorrow for those who lost loved ones on 9-11" while reminding the public that terrorists were the ones responsible, White House spokesman Dan Bartlett said.
Bartlett also said the significance of the hearing was being overstated. "We have every level of confidence in our actions before 9-11 and particularly our actions afterward," he said. "We don't believe the stakes are as high as people are suggesting them to be."
Commissioners on the 10-member bipartisan panel want to know what outgoing Clinton administration officials told Rice about terrorism. Clarke has said he gave Rice warnings in January 2001 but was put off repeatedly. Rice has said Clarke merely presented a "set of ideas" that required a more comprehensive review.
Commissioners also want to know whether the administration acted reasonably in the summer of 2001 as intelligence warnings increasingly pointed to an impending terrorist attack. In July of that year, the government issued several advisories, including to the domestic aviation industry, but said intelligence was mostly suggestive of an overseas attack.
"It's important to look as the alerts increased in the spring and summer of 2001, as the alarm bells were loudly clanging, as the CIA director was running with his hair on fire, what was the administration doing to respond?" said commission member Timothy Roemer, a former Democratic congressman from Indiana.
Republican commissioner Jim Thompson, a former Illinois governor, said he was interested in clearing up discrepancies in statements between Clarke and Rice to create a factual accounting of events leading up to Sept. 11.
"It's important to put her testimony on par with others and let the American people judge for themselves," Thompson said.
In the years since her husband perished in the World Trade Center collapse on Sept. 11, Patty Casazza has looked for answers — and now believes Rice can help provide them.
She and other relatives have long called for Rice's public testimony, saying she is a key witness in explaining how highly the Bush administration regarded the threat from al Qaeda terrorists blamed for the attacks.
"Her testimony will either undermine our confidence in this administration or bolster it," Casazza said.
Rice is not the only person who will feel pressure before the cameras.
If Sept. 11 panel members appear politically motivated in their questioning of the national security adviser, it could raise questions about their credibility — and the findings in their final report this summer.
Meanwhile, the commission said Wednesday it had requested about 1,000 pages of Clinton administration counterterrorism documents held by the White House that Bush aides had not released due to "inadvertent" error or because they weren't originally requested by the panel.
Lawyers for the commission reviewed 10,800 pages of classified documents from the Clinton administration this week after Bruce Lindsey, who was former President Clinton's legal adviser, said officials didn't turn over all of Mr. Clinton's records to the panel.
The commission plans three more public hearings and was to meet with Mr. Bush and Mr. Clinton in private before issuing a final report in July.