Tomas, a surgeon in the city of Prague in the early 1960s, meets Tereza in a small Czech town, and she comes to the city to be with him. Although they love each other and marry, he is a tireless womanizer, which upsets her and gives her nightmares. Tomas is sensitive to her pain, but he cannot stop going off with other women. One of his longtime liaisons is with Sabina, an artist and free spirit.
When the Soviet Army invades Czechoslovakia in August 1968, Tomas accepts a job in Zurich, Switzerland and Tereza follows. But, exhausted by his infidelities, she returns to Prague. Surprised by how much he misses her, Tomas follows shortly after. He gets in trouble over an article he writes about the authoritarian regime, loses his position, and becomes a window washer -- a curiously liberating position that allows him to pursue even more women over the next three years.
Sabina also escapes to Switzerland, to Geneva, where she meets Franz, a married university lecturer who falls hard for her and takes her on trips all over Europe. When he decides that Sabina’s the one for him and confesses to his wife Marie-Claude about the affair, Sabina disappears. Unable to obtain a divorce from his wife, Franz moves in with a student, “a girl with big glasses.”
Life under the Communist government and the secret police in Czechoslovakia gets steadily worse. Working as a barmaid, Tereza tries having sex with a stranger in order to get over her jealousy toward Tomas’s infidelities. It turns out to be a startling and memorable experience, but not in the way she expects or desires. Meanwhile, Tomas is tracked down by his grown son from an early, unhappy marriage; the young man wants a relationship with his father but Tomas is not enthusiastic.
Tomas and Tereza agree to escape to the country with their dog Karenin. They move to a small village where Tomas drives equipment on a collective farm and Tereza cares for the animals. The slower pace of life, where the Communist government doesn’t care enough to pry into their affairs, agrees with them.
Always fascinated by history, and inclined to take action on behalf of liberal causes, Franz decides to join a protest march into Cambodia against the Khmer Rouge. Most of the protestors are medical professionals, but some European and American celebrities tag along and draw all the media attention. Unable to enter Cambodia, the protestors return, discouraged, to Thailand. Franz is mugged in Bangkok and badly injured; returned to a hospital in Geneva, he is taken in by his estranged wife just before he dies.
Having escaped the Communists, Franz, and her many past lives by moving to Paris, New York, and California, Sabina learns by letter of the death of her old friends in a car accident. But by that time Tomas and Tereza have reached a state of contentment about the arc of their lives.