In ancient times the area was inhabited by the Donghu, Xiongnu, Xianbei, Khitan, Jurchen, Mongols and Manchu.

During the decline of China's last dynasty, the Russian Empire forced the Qing (1644–1912) to cede Outer Manchuria in the 1858 Treaty of Aigun.

Under the Republic of China, Manzhouli (under the name Lubin [臚濱; Lúbīn; Lu2-pin1]) came under the jurisdiction of the province of Hsingan.

The Russian townlet of Zabaykalsk is situated immediately north of Abagaitu Islet and Manzhouli.

Manzhouli has a semi-arid climate (Köppen (BSk), with temperatures in winter capable of plummeting below −40 °C (−40 °F).

Manzhouli Ice & Snow Festival takes place every winter from some time in February to early March.

Manzhouli is China's busiest land port of entry, and is responsible for 60% of all imports from and exports to Eastern Europe.

Much of the plot of the 2018 film An Elephant Sitting Still revolves around a number of characters traveling to a circus in Manzhouli.

A break of gauge multi-modal transshipment facility was completed in 2008 across the Russian border in Zabaikalsk.