Situated on the Syr Darya river at the mouth of the Fergana Valley, Khujand was a major city along the ancient Silk Road.

Khujand may have been the site of Cyropolis (Κυρούπολις) which was established when King Cyrus the Great founded the city during his last expedition against the Saka tribe of Massagetae shortly before his death.

[4] The city would form a bastion for the Greek settlers against the nomadic Scythian tribes who lived north of the Syr Darya River.

[6] In the early eighth century AD, Khujand was captured by the forces of the Umayyad Caliphate, under Qutayba ibn Muslim.

In 1866, as most of Central Asia was occupied by Russian Empire, the city became part of the General Governorate of Turkestan, under Tsarist Russia.

The threat of forced conscription during World War I led to protests in the city in July 1916, which turned violent when demonstrators attacked Russian soldiers.

Now a part of the Tajik SSR, Leninobad became the second-largest city in the republic, though the city's location within the historically more urban, prosperous, and commercially central Fergana Valley and a long history of being a densely populated urban centre meant that Khujand and its region were sometimes viewed as more developed and cosmopolitan than the newly designated capital and boom-town of Dushanbe/Stalinabad (the latter was a small town of 6,000 when the Tajik SSR was created in 1926 and had reached over 200,000 inhabitants ten years later).

[10] On 3 September 2010, a suicide attack was committed in the city by the al-Qaeda linked Jamaat Ansarullah militant group, resulting in the deaths of 4 people.

Kholmatov was accused of singing too loudly and "interfering with the comfort and rest" of people who lived nearby, and jailed for three years.

Previously, particularly during cold seasons, the lack of a direct link between northern and southern Tajikistan often led to disruptions of commercial activities in the region.

The city is home to the Historical Museum of Sughd located within the Khujand Fortress and having around 1200 exhibitions with most being open to the public.