In 1929 the Tajik and Uzbek Soviet socialist republics were separated. As Uzbek communist party chief, Khojayev enforced the policies of the Soviet government during the collectivization of agriculture in the late 1920s and early 1930s and, at the same time, tried to increase the participation of Uzbeks in the government and the party. Soviet leader Joseph V. Stalin suspected the motives of all reformist national leaders in the non-Russian republics of the Soviet Union. By the late 1930s, Khojayev and the entire group that came into high positions in the Uzbek Republic had been arrested and executed during the Stalinist purges.

Following the purge of the nationalists, the government and party ranks in Uzbekistan were filled with people loyal to the Moscow government. Economic policy emphasized the supply of cotton to the rest of the Soviet Union, to the exclusion of diversified agriculture. During World War II, many industrial plants from European Russia were evacuated to Uzbekistan and other parts of Central Asia. With the factories came a new wave of Russian and other European workers. Because native Uzbeks were mostly occupied in the country's agricultural regions, the urban concentration of immigrants increasingly Russified Tashkent and other large cities. During the war years, in addition to the Russians who moved to Uzbekistan, other nationalities such as Crimean Tatars, Chechens, and Koreans were exiled to the republic because Moscow saw them as subversive elements in European Russia.