After a number of years, Avraham died and his younger brother, Rabbi Chaim Leib Tiktinsky, succeeded him.

In 1921, the yeshiva moved back to its original facilities in Mir, where it remained until, based on secret parts of the Molotov–Ribbentrop Pact, Nazi Germany and the Soviet Union invaded Poland in 1939.

The yeshiva moved en masse on October 15 to Vilna in order to get out from under Russian rule and into then-free Lithuania.

Around this time, Rabbi Eliezer Yehuda Finkel traveled to Palestine to obtain visas for his students and reestablish the yeshiva in Eretz Yisrael, but these plans were interrupted by the outbreak of World War II.

[11] In Europe, as the Nazi armies continued to push to the east, the yeshiva students fled to (Japanese-controlled) Shanghai, China, where they remained until the end of the war.

The story of the escape to the Far East of Mir Yeshiva, along with thousands of other Jewish refugees during WWII, thanks largely to visas issued by the Dutch consul Jan Zwartendijk and the Japanese consul-general to Lithuania, Chiune Sugihara, has been the subject of several books and movies including the PBS documentary Conspiracy of Kindness.

Reb Chaim was considered the main Rosh Yeshiva and when he died, his son-in-law, Rabbi Nachum Partzovitz, replaced him.