These are all firsts.
Mr. Bush has never before given a visiting leader the honor of picking him up at the airport. In fact, no president has done so at Andrews Air Force Base, the typical landing spot for modern leaders.
A crowd of up to 12,000 is due at the White House on Wednesday morning for the pope's official, pomp-filled arrival ceremony. It will feature the U.S. and Holy See anthems, a 21-gun salute, and the U.S. Army Old Guard Fife and Drum Corps. Both men will make remarks before their Oval Office meeting and a send-off for his popemobile down Pennsylvania Avenue.
The White House crowd will be the largest of Mr. Bush's presidency. It even beats the audience last spring for Britain's Queen Elizabeth II, which numbered about 7,000.
The evening festivities will mark the first time the Bushes have put on a high-profile meal in honor of someone who is not even a guest. Wednesday is the pontiff's 81st birthday, and the menu celebrates his German heritage with Bavarian-style food.
But Benedict's prayer service that evening with U.S. bishops at a famed Washington basilica precludes him from coming to the dinner, according to the White House. Catholic leaders will be there instead.
The president explained the special treatment - particularly the airport greeting.
"One, he speaks for millions. Two, he doesn't come as a politician; he comes as a man of faith," Mr. Bush told the EWTN Global Catholic Network in an interview aired Friday. He added that he wanted to honor Benedict's conviction that "there's right and wrong in life, that moral relativism has a danger of undermining the capacity to have more hopeful and free societies."
One senior Vatican official told CBS News correspondent Allen Pizzey that the pope's six-day visit to Washington and New York will be like a pilgrimage to the soul of the American people.
The Bush-Benedict get-together will be the 25th meeting between a pope and a sitting U.S. president.
The first did not come until shortly after the end of World War I, when Woodrow Wilson was received at the Vatican by Pope Benedict XV in 1919. The next was not for 40 more years, when President Dwight D. Eisenhower saw Pope John XXIII in Rome. President Jimmy Carter hosted the first White House visit by a pope, when John Paul II came on Oct. 6, 1979.
Since then, such audiences have become a must-do. Every president has met with the pope at least once, often more. This week makes Mr. Bush the record-holder, with a total of five meetings with two popes.
There are more than 64 million reasons for this. Catholics number nearly one-quarter of the U.S. population, making them a desirable constituency for politicians to court. Worldwide, there are now an estimated 1 billion Roman Catholics.
"The pope represents not just the Catholic church but the possibility of moral argument in world affairs and it is very important for American presidents to rub up against that from time to time," said George Weigel, a Catholic theologian and biographer of Pope John Paul II.
The Vatican - seat of a government as well as a religious headquarters - has an interest, too.
"It wants to be a player in world affairs, and everyone understands that to do that you have to be in conversation with the United States," said John Allen, the Vatican correspondent for the independent National Catholic Reporter.
On social issues such as abortion, gay marriage and stem cell research, Mr. Bush and Benedict have plenty of common ground.
But they disagree over the war in Iraq, just as Mr. Bush did with Benedict's predecessor, John Paul.
When Benedict was a cardinal before the 2003 invasion, the now-pontiff categorically dismissed the idea that a preventive strike against Iraq could be justified under Catholic doctrine. In his Easter message last year, Benedict said "nothing positive comes from Iraq."
Benedict told Mr. Bush at their first meeting last summer at the Vatican that he was concerned about "the worrisome situation in Iraq." Mr. Bush characterized the pontiff's concerns as mostly limited to the treatment of the Christian minority in Muslim-majority Iraq. The statement out of the Vatican suggested a broader discussion.
Weigel predicted talks this time would be focused almost entirely there.
Prominent Christians have been slain in Iraq in recent weeks and tens of thousands of Iraqi Christians are believed to have fled the country because of attacks and threats. "The Vatican is a very adult place," he said. "The arguments of five years ago are over."
The current pope's approach may be softer than that of John Paul, who turned from Mr. Bush's presentation to him of the Medal of Freedom in 2004 to read a statement about his "grave concern" over events in Iraq. But Benedict is no less committed to the church's stand on issues such as abortion, stem cell research and the death penalty, as well as war.
In fact, the death penalty is another area of long-held disagreement, with Mr. Bush a strong supporter. Benedict also speaks forcefully against punitive immigration laws and the U.S. trade embargo against Cuba, and for environmental protection and social welfare - all in ways that often run counter to Bush administration policies.
But differences between popes and presidents are nothing new.
John Paul and former President Bill Clinton clashed - with strikingly sharp Vatican statements - on abortion.
Also, the church's opposition to almost any war but self-defensive ones has been a persistent theme in U.S. relations.
Pope Paul VI wanted to help mediate an end to the Vietnam War. John Paul also urged President Ronald Reagan against the arms race and spoke out vigorously against the Persian Gulf war under the current president's father. All these urgings, like the current anti-Iraq argument, were to no avail.
"Modern popes have seen themselves as voices of conscience and peacemakers," Allen said. "U.S. administrations haven't always been excited for them to play that role."
Weighty discussions aside, the talks with Mr. Bush are not likely to be the most-remembered or most influential part of the pontiff's six-day, two-city U.S. tour, Weigel said. That is expected to come when Benedict addresses the United Nations on Friday.
"I think it's nice they're going to meet. They have a lot of things to talk about," he said. "But the notion that the world operates by the big guys getting together and cutting a deal is wrong."