The first year of the story is 2073 in England. Lionel Verney and Perdita Verney are siblings who struggle to survive after the death of their parents. Adrian, the Earl of Windsor, discovers them and gives them a place to live.

Raymond is in love with Perdita and asks her to marry him. She loves Raymond intensely, and they marry. Lionel deeply loves Adrian's sister Idris, and when she comes to Lionel to save her from being taken to Germany, he rescues her and they marry. Adrian has been ill in Scotland since Evadne left England, but he returns to England and regains his health.

The extended family lives together for five happy years. Children are born to the couples, and their lives are blissful. When it is time for a new Lord Protector of England to be elected, Raymond decides to leave Windsor with his family to live in London. He becomes the new Lord Protector, and he is full of plans to improve the country. But he grows bored, and his life begins to fall apart. He leaves for Greece with Adrian, and when Perdita learns that Raymond is missing in Greece, she immediately leaves to find him. Lionel goes with her.

Lionel Verney, Perdita Verney, and Raymond's daughter Clara go to Greece to find Raymond. He wants to retake command of the Greek army and defeat the Turks who rule over Greece. He leads the army to victory in Rodosto and then proceeds to Constantinople to claim that city for the Greeks. The plague has entered the city, and all its inhabitants are dead. Raymond enters the city to place the Greek flag at the top of St. Sophia, but he dies from the plague. His wife commits suicide.

When Lionel and Clara return to England, life at Windsor proceeds without immediate threat from the plague. Adrian becomes energized and takes over the protectorate. He encourages the aristocracy to allow their lands to be farmed for food. When the plague reaches Italy and France, immigrants come north to England. Lionel and his family take care of many of them at Windsor. The approach of summer in England inspires a decision in Lionel. He wants to take his family south and out of England.

Many English people arrive at the coast to go to France, but there is a storm that detains them for three days. A group of English people arrives from Paris to tell them they should not go there. In Paris there are only about a hundred survivors. Adrian, Lionel, and their group of about 1,500 survivors leave Versailles for a colder climate where they believe the plague will not be as virulent. They travel to Switzerland, but by the time they reach the Alps there are only 50 people remaining in the group. There are no survivors in Switzerland. The plague has lasted for seven years. Eventually, there are only four remaining survivors including Lionel, Adrian, Clara, and Evelyn. The four of them travel to Lake Como in Italy where Evelyn dies. Lionel, Adrian, and Clara leave Lake Como for Rome.

The three survivors travel through Venice and decide to go by boat to Greece instead of going to Rome. There is a ferocious storm, and Adrian and Clara drown. Lionel is able to swim to shore. He realizes he is the last man on earth.