German forces entered Kaunas on June 24, 1941, two days after Operation Barbarossa began. Before the Wehrmacht arrived, members of the Lithuanian Activist Front and other anti-Communist Lithuanian groups had already begun killing Jewish residents in the streets, blaming them collectively for Soviet repressions of the prior year. The Kaunas pogrom of late June 1941 killed thousands. By August 15, the Germans had concentrated the surviving Jewish population—about twenty-nine thousand people—into the working-class suburb of Vilijampolė, known to Yiddish-speaking residents as Slabodka, on the right bank of the Neris River. The Lithuanian commandant Jurgis Bobelis had approved the ghetto's establishment. Lithuanian auxiliary police, organized into the TDA battalions, would aid Nazi units in the killings that followed. Telling this history honestly means naming Lithuanian collaboration without sliding into a story of national guilt; not every Lithuanian collaborated, many resisted, and a number risked everything to hide Jewish neighbors. But the truth includes that significant Lithuanian collaboration in the killing happened, and Jewish survivors named it.

On October 28, 1941, the SS officer Helmut Rauca ordered the entire ghetto population to gather on Demokratu Square. Thousands of people stood through a freezing day while Rauca, sometimes eating sandwiches as he worked, sorted them with a flick of his wrist: left lived, right died. Of the people sent right, more than nine thousand were marched the next morning to the Ninth Fort and shot in pits prepared in advance. Survivors who were sent left would later remember the choice between fates that took only a moment to make and that often turned on which family member you were standing beside. This was the Great Action. Two earlier 'actions' had killed nearly three thousand Jewish people at the Seventh Fort in early July and over eighteen hundred intellectuals at the Fourth Fort in August. The Great Action was the largest single day of killing the Kaunas ghetto would experience.

From 1942 the Nazis forbade births in the ghetto. Pregnancy meant death. Yet Jewish parents and Lithuanian foster mothers organized a smuggling operation that would later be remembered as the babies in potato sacks—infants between roughly nine and fifteen months old, drugged so they would not cry, hidden inside burlap and carried out of the ghetto to families willing to risk their own lives raising them as their own. The orchestrator was the Jewish Council, working with a network of Lithuanian rescuers. Inside the ghetto, life held on in the spaces it could find. An orchestra of imprisoned musicians performed about eighty-three concerts, mostly in the building of the former Slabodka Yeshiva, which before the war had been one of the most prestigious centers of higher Jewish learning in Europe. The composer Percy Haid, born in Riga, wrote much of its music. People studied in underground schools. The ghetto's children read books in clandestine classrooms knowing that the punishment for an unauthorized class was death.

March 27 and 28, 1944. Police vans rolled through the ghetto streets blaring music over loudspeakers to drown out the screams of families. Roughly sixteen hundred children aged twelve and younger, and their parents who tried to intervene, and around nine hundred elderly people aged fifty-five and older—approximately twenty-five hundred people in total—were rounded up and murdered in what survivors call the Kinder Aktion. Forty Jewish ghetto policemen who had refused under torture by the SS officer Bruno Kittel to disclose hidden children were also killed. Some parents had been warned by reports of similar actions at other ghettos and managed to smuggle their children out to non-Jewish foster homes in the days before. The vast majority did not have time. By the time Kovno was liberated, very few Jewish children remained alive.

In autumn 1943 the SS converted the ghetto into the Kauen concentration camp under the commandant Wilhelm Göcke. The Jewish Council was largely stripped of its remaining authority. Thousands were dispersed to subcamps. On October 26, 1943, more than twenty-seven hundred people were deported—those deemed fit to work to Vaivara concentration camp in Estonia, children and elderly people to Auschwitz. On July 8, 1944, with Soviet forces approaching, the Germans evacuated the camp, deporting most of the remaining Jewish population to Dachau in Germany or to Stutthof on the Baltic coast near Danzig. Three weeks before the Red Army arrived in Kaunas, the Germans set the ghetto on fire and dynamited its buildings to deny survivors any cover. As many as two thousand people who were hiding burned to death or were shot trying to escape the flames. The Soviets entered Kaunas on August 1, 1944. About five hundred Jewish residents had survived in the forests with partisans, and a single bunker that had escaped detection during the final liquidation gave shelter to a handful more.

Aharon Barak, smuggled out of the ghetto by a Lithuanian farmer as a child, became President of the Supreme Court of Israel from 1995 to 2006. Avraham Tory recovered his diary from its hiding place after the war and lived to see it published in Cambridge in 1990 as Surviving the Holocaust. The hidden archives George Kadish photographed were dug up after liberation; his images of ghetto life now hang in the United States Holocaust Memorial Museum's permanent exhibition. The General Jewish Fighting Organization, formed in 1943, helped roughly three hundred ghetto fighters escape to join Soviet partisans in the forests; about seventy died in action. Of the twenty-nine thousand people who entered the Kovno Ghetto in 1941, fewer than two thousand are estimated to have survived the war. Their stories—written in secret, photographed through buttonholes, painted in watercolor for children who would not live to see the painting finished—are among the most complete personal records of any community the Holocaust destroyed. The community itself was not saved. Its memory was.