The White House announced Mr Biden’s trip on Tuesday, following months of deliberations. Mr Biden's visit to Saudi Arabia is his first to an Arab country since he became president last year.
The trip to the Middle East from July 13 to16 will “reinforce the United States’ ironclad commitment to Israel’s security and prosperity,” White House Press Secretary Karine Jean-Pierre said.
She said Mr Biden would attend a summit of the Gulf Co-operation Council plus Egypt, Iraq, and Jordan, known as the GCC+3.
He is expected to meet Saudi leader King Salman and Crown Prince Mohammed bin Salman, a senior US official said.
The trip begins in Israel and the West Bank, where Mr Biden's agenda is expected to focus on security and the two-state solution.
He will also meet Israeli leaders “to discuss Israel’s security, prosperity, and its increasing integration into the greater region”, the White House said.
He will then meet Palestinian President Mahmoud Abbas and “reiterate his strong support for a two-state solution, with equal measures of security, freedom, and opportunity for the Palestinian people”.
In Israel, Mr Biden is also planning to visit an area where US defence systems, such as the Iron Dome, are installed, the senior US official said.
He will also host a four-way online meeting with the leaders of Israel, the UAE and India, members of what is known as the “West-Asian Quad” to discuss innovation and food security.
“The president looks forward to this unique engagement with Prime Minister [Naftali] Bennett of Israel, Prime Minister [Narendra] Modi of India and President Mohamed bin Zayed of the UAE,” the official said.
From Israel, Mr Biden will fly to Jeddah, for a gathering of GCC leaders.
The focus for the Saudi stop will be regional, economic and security co-operation, deterring threats from Iran, advancing human rights, and ensuring global energy and food security, the White House said.
“The president looks forward to outlining his affirmative vision for US engagement in the region over the coming months and years,” Ms Jean-Pierre said.
Mr Biden will make it “clear that the United States is fully committed to supporting the territorial defence of our partners against threats from Iran or elsewhere,” the senior official said.
The Saudi Press Agency reported that Mr Biden will meet King Salman and Crown Prince Mohammed to discuss aspects of co-operation between the two “friendly” countries and ways to address the challenges facing the region and the world.
Mr Biden will attend a summit called by the Saudi King with the leaders of the GCC countries along with Jordan's King Abdullah II, Egyptian President Abdel Fattah El Sisi and Iraq’s Prime Minister Mustafa Al Kadhimi.
The trip comes as the Biden administration continues to expand co-operation with Riyadh. This includes seeking an end to the war in Yemen.
A UN-brokered truce between Yemen's warring parties was extended this month and Mr Biden praised Saudi Arabia for its role.
For the past year and a half, however, US-Saudi tension has increased over the killing of Saudi journalist Jamal Khashoggi and Riyadh's refusal to increase oil supplies.
US officials stress that they want to avoid a “rupture” in the relationship, and “to move forward as partners”.
Mr Biden’s predecessors, Donald Trump and Barack Obama, visited Saudi Arabia in their first year in office.