The visit reflects the pontiff's tendency to visit countries on the periphery that have faced many historic and social challenges.
On Saturday, the head of the Roman Catholic Church is scheduled to meet with Lithuania's leaders and pray at the Gate of Dawn chapel before meeting with young people in the capital's Cathedral Square in the evening.
On Sunday, the pope will go to Kaunas to celebrate Holy Mass in the city's Santakos Park and will travel back to Vilnius later in the day to visit a monument to the victims of the Vilnius Ghetto and the Museum of Occupations and Freedom Fights.
The world will have its eyes set on the pope visiting Lithuania this weekend to see if he will touch upon the sexual abuse scandal rocking the Catholic Church.
Shocking figures revealed in the United States and Europe over the past few months have revealed the scale of sexual abuse against children by Catholic priests or attempts to cover them up.
Traffic restrictions will be in place in Vilnius' Old Town on Saturday and in Kaunas' Old Town on Sunday.
Francis' Baltic tour comes 25 years after Pope John Paul II visited the three countries in 1993.