Traditionally the "football", a briefcase that contains the codes and mechanisms needed for a president to authorise a nuclear strike, is symbolically handed from one military aide to a new designated aide at midday - when the new commander-in-chief is sworn in.
But on Wednesday the exchange will occur in an unusual way, with Mr Trump expected to quit Washington for his private beach club in Florida before Mr Biden is sworn in as the next president.
It is expected that multiple nuclear "footballs" could be in use today, with one travelling Mr Trump on Air Force One to Florida, one accompanying Mr Biden in Washington, another accompanying the vice president and one assigned to a designated survivor.
Contrary to popular belief, the nuclear "football" does not contain a button or code that immediately launches an attack.
Rather, it contains the equipment necessary for a president to communicate with military commands and authorise an attack while away from the White House.
A key component included within the black leather briefcase is the "biscuit", an electronic card which contains the codes needed to identify the president as the person able to authorise a nuclear attack.
Mr Biden will receive his "biscuit" on Wednesday morning when he and his vice president, Kamala Harris, are briefed on the process of initiating a nuclear strike.
However Mr Biden and Ms Harris' codes will not become active until noon on Wednesday, the time outlined in the US Constitution when a new president takes office.
Up until that point, Mr Trump will have the sole power to launch a nuclear strike. Mr Trump's "biscuit" containing his codes will become deactivated at noon.
It brings to an end Mr Trump's control over the codes needed to launch a US nuclear strike after four tumultuous years in office.
Mr Trump's sole authority to order a nuclear attack has been a major talking point throughout his presidency, with critics at times concerned that his volatile relationships with North Korea, Iran and other states could lead him to order a nuclear strike.
In the wake of his role in the Capitol riots, Nancy Pelosi, the Democratic House Speaker, even sought assurances from the country's top general that an "unstable" Mr Trump would be unable to order a nuclear strike.
Ms Pelosi later told her party that she had received assurances that there were safeguards in place for the process of launching a nuclear attack.