In front of around 200 nuns, priests, cardinals and other Christians, the pontiff lay flat on the floor in front of the altar in St Peter's Basilica for several minutes, as is traditional on Good Friday.
Due to the pandemic, only a limited number of people were admitted to the Mass, as was the case a year earlier.
Early in the day, the pope visited health workers in the Vatican's coronavirus vaccination centre, where the Pfizer/BioNTech vaccine is being administered, according to the Holy See.
The 84-year-old, who has already been immunized against Covid-19, greeted the workers and talked to people awaiting their vaccination.
Before Easter, the Vatican announced that it would vaccinate 1,200 people in need during the holiday. So far, about 800 of them have received their first vaccine dose.
The large public Stations of the Cross at the Colosseum in the centre of Rome, which used to be a moving event for the thousands of pilgrims who showed up, was cancelled as in 2020.
Small Stations of the Cross
Instead - similar to the beginning of the pandemic - a small Stations of the Cross celebration took place in St Peter's Square in front of the basilica at 9 pm.
The event traditionally re-enacts Jesus' journey to death on the cross. This time, children and young people wrote texts and drew pictures before hand that were then placed at each of the 14 stations.
At night, a path was laid out with candles to St Peter's Basilica, which a few young people and children walked along, accompanied by nuns.
After each of the 14 reflections were read by a child, the pope responded with a prayer. The texts included thoughts on the pandemic and even the Mafia.
For the 84-year-old Francis, it is the second Holy Week and Easter under severe coronavirus restrictions.
Easter, as the celebration of the resurrection of Jesus, is the most important religious festival for Christians.