Her visit to Cuba is the latest sign of the rapprochement between the Cold War foes following President Barack Obama's visit in March.
Biden was greeted at Havana's international airport by Josefina Vidal, who is leading negotiations with the United States as head of U.S. affairs at the Cuban Foreign Ministry.
Biden plans to watch a match between the U.S. and Cuban soccer teams on Friday in Havana, go on social media at one of Cuba's new WiFi hot spots and visit a teachers college, among other activities, according to U.S. diplomatic sources in Havana.
Ambassador-at-Large for Global Women's Issues Cathy Russell and Assistant Secretary of State for Educational and Cultural Affairs Evan Ryan are accompanying Biden, who will also travel to central Camaguey province before heading to the Dominican Republic on Sunday.
A White House statement said Biden, herself an educator, was scheduled to meet with "government officials and engage with a diverse range of Cubans on topics related to culture, education, and health."
The Obamas' visit highlighted the warming trend in bilateral relations announced by both countries in December 2014 after 18 months of secret talks and more than a half-century's estrangement.
Some U.S. lawmakers strongly oppose the move, arguing that Communist-ruled Cuba must do far more to improve human rights before it can deal normally with the United States.
Agreements have been reached in areas such as law enforcement, the environment, resumption of postal service and commercial flights, while talks on such thorny issues as fugitives and reparations continue.
The decades-long U.S. trade embargo on Cuba remains in place and can only be lifted by Congress, although Obama has used his executive authority to chip away at it.
Both sides have said they want to strengthen their economic relationship, but the United States has complained the Cubans have been slow to take advantage of openings carved out by Obama, for example, trade with the private sector, while Cuba says U.S. sanctions make most trade and investment impossible.
U.S. Trade Representative Michael Froman is also in Havana where he is scheduled to meet on Friday with Foreign Minister Bruno Rodriguez and Foreign Trade and Investment Minister Rodrigo Malmierca.