Rapid growth of the city challenged the public healthcare system. The worst-ever recorded outbreak of pneumonic plague was spread to Harbin through the Trans-Manchurian railway from the border trade port of Manzhouli. The plague lasted from late autumn of 1910 to spring 1911 and killed 1,500 Harbin residents (mostly ethnic Chinese), or about five percent of its population at the time. This turned out to be the beginning of the large pneumonic plague pandemic of Manchuria and Mongolia which ultimately claimed 60,000 victims. In the winter of 1910.

After the plague epidemic Harbin's population continued to increase sharply, especially inside the Chinese Eastern Railway Zone.

In 1913 the Chinese Eastern Railway census showed its ethnic composition as: Russians – 34313, Chinese (that is, including Hans, Manchus etc.) – 23537, Jews – 5032, Poles – 2556, Japanese – 696, Germans – 564, Tatars – 234, Latvians – 218, Georgians – 183, Estonians – 172, Lithuanians – 142, Armenians – 124; there were also Karaims, Ukrainians, Bashkirs, and some Western Europeans. In total, 68549 citizens of 53 nationalities, speaking 45 languages. Research shows that only 11.5 percent of all residents were born in Harbin.

By 1917, Harbin's population exceeded 100,000, with over 40,000 of them were ethnic Russians.

After Russia's Great October Socialist Revolution in November 1917, more than 100,000 defeated Russian White Guards and refugees retreated to Harbin, which became a major center of White Russian émigrés and the largest Russian enclave outside the Soviet Union.The city had a Russian school system, as well as publishers of Russian-language newspapers and journals. Russian Harbintsy
community numbered around 120,000 at its peak in the early 1920s. In the early 1920s, according to Chinese scholars' recent studies, over 20,000 Jews lived in Harbin.

The Republic of China discontinued diplomatic relations with the Soviet Union in 1920, so many Russians found themselves stateless. When the Chinese Eastern Railway and government in Beijing announced in 1924 that they agreed the railroad would only employ Russian or Chinese nationals, the emigrees were forced to announce their ethnic and political allegiance. Most accepted Soviet citizenship.

When Vladivostok fell to the Bolsheviks on October 25, 1922, the civil war essentially came to a close, and White families fled towards the nearby Chinese border in fear of their lives. The obvious destination was Harbin, which had been a pseudo-Russian colony since 1898, administered by engineers and officials appointed by the tsarist regime to build and operate the Chinese Eastern Railway (CER) under a concession granted by Qing China. (Significant numbers of White Russians had also settled in what is now Xinjiang.)

Harbin offered a comfortable refuge for fleeing Whites and the city also became the de facto home of the Russian Orthodox Church.
“The Russian church and immigrants enjoyed total free­dom in China,” says Denis Pozdnyaev, pointing out there were once more than 100 Russian churches in China, inclu­ding 23 in Harbin. However, the good times for the 150,000 Russians living in the CER zone were to be short-lived.
In 1924, when Peking finally recognised the new Soviet government, old Russian passports were invalidated and those who rejected the chance to become Soviet citizens – the vast majority of Whites – became stateless.
The Russians were treated as social outcasts by many among the European elite.

Japan invaded Manchuria outright after the Mukden Incident in September 1931. After the Japanese captured Qiqihar in the Jiangqiao Campaign, the Japanese 4th Mixed Brigade moved toward Harbin, closing in from the west and south.
Bombing and strafing by Japanese aircraft forced the Chinese army to retreat from Harbin. Within a few hours the Japanese occupation of Harbin was complete.

With the establishment of the puppet state of Manchukuo, the pacification of Manchukuo began, as volunteer armies continued to fight the Japanese.

 Harbin became a major operations base for the infamous medical experimenters of Unit 731, who killed people of all ages and ethnicities. All these units were known collectively as the Epidemic Prevention and Water Purification Department of the Kwantung Army.The main facility of the Unit 731 was built in 1935 at Pingfang District, approximately 24 km (15 mi) south of Harbin urban area at that time. Between 3,000 and 12,000 citizens including men, women, and children—from which around 600 every year were provided by the Kempeitai—died during the human experimentation conducted by Unit 731 at the camp based in Pingfang alone, which does not include victims from other medical experimentation sites.
Almost 70 percent of the victims who died in the Pingfang camp were Chinese, including both civilian and military. Close to 30 percent of the victims were Russian. Some others were South East Asians and Pacific Islanders, at the time colonies of the Empire of Japan, and a small number of the prisoners of war from the Allies of World War II (although many more Allied POWs were victims of Unit 731 at other sites). Prisoners of war were subjected to vivisection without anesthesia, after infected with various diseases.
Prisoners were injected with inoculations of disease, disguised as vaccinations, to study their effects. Unit 731 and its affiliated units (Unit 1644 and Unit 100 among others) were involved in research, development, and experimental deployment of epidemic-creating biowarfare weapons in assaults against the Chinese populace (both civilian and military) throughout World War II. Human targets were also used to test grenades positioned at various distances and in different positions. Flame throwers were tested on humans. Humans were tied to stakes and used as targets to test germ-releasing bombs, chemical weapons, and explosive bombs. Twelve Unit 731 members were found guilty in the Khabarovsk War Crime Trials but later repatriated; others received secret immunity by the Supreme Commander of the Allied Powers Douglas MacArthur before the Tokyo War Crimes Tribunal in exchange for biological warfare work in the Cold War for the American Force.

Under the Manchukuo régime and Japanese occupation, Harbin Russians had a difficult time. In 1935, the Soviet Union sold the Chinese Eastern Railway (KVZhD) to the Japanese, and many Russian emigres left Harbin (48133 of them were arrested during the Soviet Great Purge between 1936 and 1938 as "Japanese spies"Most departing Russians returned to the Soviet Union, but a substantial number moved south to Shanghai or emigrated to the United States and Australia.

By the end of the 1930s, the Russian population of Harbin had dropped to around 30,000.

Many of Harbin's Jews (13,000 in 1929) fled after the Japanese occupation as the Japanese associated closely with militant anti-Soviet Russian Fascists, whose ideology of anti-Bolshevism and nationalism was laced with virulent anti-Semitism. Most left for Shanghai, Tianjin, and the British Mandate of Palestine.

The Soviet Army took the city on 20 August 1945 and Harbin never came under the control of the Kuomintang, whose troops stopped 60 km (37 mi) short of the city.
 
The city's administration was transferred by the departing Soviet Army to the Chinese People's Liberation Army in April 1946.

On 28 April 1946, the Communist Government of Harbin was established, making the 700,000-citizen-city the first large city under Chinese Communist force rule.
During the short occupation of Harbin by the Soviet Army (August 1945 to April 1946), thousands of Russian emigres who have been identified as members of the Russian Fascist Party and fled communism after the Russian October Revolution, were forcibly deported to the Soviet Union.
After 1952 the Soviet Union launched a second wave of immigration back to Russia. By 1964, the Russian population in Harbin had been reduced to 450. The rest of the European community (Russians, Germans, Poles, Greeks, etc.) emigrated during the years 1950–54 to Australia, Brazil, Canada, Israel and the USA, or were repatriated to their home countries.

By 1988 the original Russian community numbered just thirty, all of them elderly.

Modern Russians living in Harbin mostly moved there in the 1990s and 2000s, and have no relation to the first wave of emigration.