The president takes pride in his Catholic faith, using it as moral guidepost to shape many of his social and economic policies.
He wears a rosary and frequently attends Mass, yet his support of abortion rights and same-sex marriage has put him at odds with many US bishops, some of whom have suggested he should be denied Communion.
White House press secretary Jen Psaki, in previewing the visit, said she expects a "warm and constructive dialogue" between the two leaders.
"There's a great deal of agreement and overlap with the president and Pope Francis on a range of issues: poverty, combating the climate crisis, ending the COVID-19 pandemic," she said.
"These are all hugely important, impactful issues that will be the centrepiece of what their discussion is when they meet."
National security adviser Jake Sullivan said the president and pontiff would meet privately, then hold talks with expanded delegations.
Mr Biden is visiting Rome to attend the G20 summit this weekend, before travelling to Glasgow for COP26.
Climate change is expected to dominate conversations at the meeting of 20 world leaders, and the decisions made at the summit may influence the decisions made a few days later at COP26.
However, the leaders may face difficulties in showing a united front against climate change - many expect division over some issues, such as the phasing out of coal.