Biden will be welcomed on the tarmac by British Prime Minister Rishi Sunak, who is looking to break political deadlock in the UK province which, alongside security concerns, threaten to overshadow the historic milestone.
Underlining the threat, masked youths pelted police vehicles with petrol bombs on Monday during an illegal march by dissident pro-Irish republicans in Londonderry, known to nationalists as Derry.
Despite the concerning scenes -- which have played out on other occasions in recent years in Northern Ireland as political tensions simmer -- US officials said Biden was "very excited for this trip".
"President Biden cares deeply about Northern Ireland and has a long history of supporting peace and prosperity there," White House National Security Council spokesman John Kirby told reporters Monday.
Biden will deliver remarks Wednesday at Ulster University in Belfast, "marking the tremendous progress" since the signing of the 1998 Good Friday Agreement.
He will also meet Northern Ireland's main political parties, according to UK media, with reports he will press the pro-UK Democratic Unionist Party (DUP) to resume power-sharing.
A key plank of the peace accords, the devolved government in Belfast collapsed 14 months ago over the party's trenchant opposition to post-Brexit trade arrangements in Northern Ireland.
Biden, who has Irish ancestry, will then travel south to Ireland for a three-day visit, in part tracing his family history.
He will deliver an address to Ireland's parliament and "celebrate the deep, historic ties" the country shares with the United States, the White House has said.
Northern Ireland has been significantly reshaped since pro-UK unionist and pro-Irish nationalist leaders struck an unlikely peace deal on April 10, 1998 -- Good Friday, two days before Easter -- following marathon negotiations.
Brokered by Washington and ratified by London and Dublin, the agreement largely ended three decades of deadly sectarian conflict in the province and intermittent attacks on mainland Britain.
The so-called Troubles left more than 3,500 people dead. They pitted Northern Ireland's then-majority Protestant unionists, wanting continued British rule, against Catholic republicans demanding equal rights and reunification with the Republic of Ireland.
But a quarter-century on, the post-Brexit trading situation and demographic shifts are prompting fresh political instability and violence by dissident republicans.
"While it is time to reflect on the solid progress we have made together, we must also recommit to redoubling our efforts on the promise made in 1998 and the agreements that followed," said Sunak to mark Monday's anniversary.
The issue is close to Biden's heart given his Irish heritage.
He will meet Irish President Michael Higgins and the Taoiseach (prime minister) Leo Varadkar on Thursday, when he will also take part in peace ceremonies, address the Irish parliament and attend a banquet dinner at Dublin Castle.
During a trip to County Mayo in northwest Ireland on Friday, Biden will visit his ancestral hometown of Ballina and meet distant cousins.
The US president is due to address thousands in the place that his family left in the mid-19th century -- when the country was ravaged by famine -- before eventually settling in blue-collar Scranton, Pennsylvania.
Biden heads home Friday, with Northern Ireland continuing its peace accord commemorations the following week, including a three-day conference starting April 17 hosted by former US secretary of state Hillary Clinton.
Her husband, Bill Clinton, played a pivotal role in securing the 1998 deal as US president from 1993 to 2001.
In the years after 1998, Northern Irish paramilitaries were disarmed, its militarised border was dismantled, and British troops departed.
The peace process, however, is perhaps more precarious now than it has been at any point since then.
The security situation has deteriorated, and UK security services last month raised the province's terror threat level to "severe".
Meanwhile, despite the UK and European Union agreeing in February to overhaul Northern Ireland's contentious post-Brexit trade terms, that new deal -- the Windsor Framework -- is yet to win DUP support.
That is seen as crucial in paving the way for a resumption of power-sharing.
But ex-British prime minister Tony Blair, who helped craft the 1998 peace deal, on Tuesday cautioned Biden against overly pressuring the party when in Belfast.
"If you try to pressurise them to do something they are fundamentally in disagreement with it's usually futile pressure, even if it comes from the US," he told the BBC.