Carter's visit comes amid a dispute between Washington and Havana over an imprisoned U.S. contractor on the island.
Alan Gross was arrested in December 2009 while working for Maryland-based Development Alternatives Inc. on a USAID-backed democracy-building project.
Gross's stated plan was to improve internet access for Cuba's small Jewish community. Jewish leaders in Cuba, however, have denied working with him. Gross was convicted and sentenced to 15 years in prison in early March for crimes against the state for bringing illegal telecommunications equipment into the country.
Carter was scheduled to meet with Jewish leaders during his trip.
Carter is also expected to meet with President Raul Castro, other government officials and Roman Catholic Cardinal Jaime Ortega before leaving on Wednesday.
The trip is under the auspices of the Carter Center, at the invitation of the Cuban government, and it is not an official U.S. mission.
Still, both the State Department and Gross' family have expressed hope that Carter's trip may help facilitate the contractor's release.
Cuba calls Gross a mercenary working on a program paid for by Washington that aimed to bring down Cuba's socialist system, and it has presented him as evidence of U.S. intentions to unleash a "cyberwar" to destabilize the island.
U.S. officials say no rapprochement between the Cold War enemies is possible while Gross remains jailed.
Washington and Havana have not had formal diplomatic relations since the 1960s, and the United States maintains economic and financial sanctions on the island.
Carter visited Cuba in May 2002 on a six-day tour during which he met with then-President Fidel Castro and criticized both Washington's embargo and the lack of political plurality on the island.
The Associated Press contributed to this report.