The Musahiban family started with his older brother, Sultan Muhammad Khan, nicknamed "Telai", meaning "golden", a nickname he was given because of his love of fine clothing. This brother was the ruler of Peshawar.
Dost Mohammad Khan was born to an influential family on 23 December 1793 in Kandahar, Durrani Empire. His father, Payindah Khan, was chief of the Barakzai Tribe and a civil servant in the Durrani dynasty. Their family can be traced back to Abdal (the first and founder of the Abdali tribe), through Hajji Jamal Khan, Yousef, Yaru, Mohammad, Omar Khan, Khisar Khan, Ismail, Nek, Daru, Saifal, and Barak. Abdal had Four sons, Popal, Barak, Achak, and Alako. Dost Mohmmad Khan's mother is believed to have been a Shia from the Azerbaijani Qizilbash group.
His elder brother, the chief of the Barakzai, Fatteh Khan, took an important part in raising Mahmud Shah Durrani to the sovereignty of Afghanistan in 1800 and in restoring him to the throne in 1809. Dost Mohammad accompanied his elder brother and then Prime Minister of Kabul Wazir Fateh Khan to the Battle of Attock against the invading Sikhs. Mahmud Shah repaid Fatteh Khan's services by having him assassinated in 1818, thus incurring the enmity of his tribe. After a bloody conflict, Mahmud Shah was deprived of all his possessions but Herat, the rest of his dominions being divided among Fatteh Khan's brothers. Of these, Dost Mohammad received Ghazni, to which in 1826 he added Kabul, the richest of the Afghan provinces.
From the commencement of his reign he found himself involved in disputes with Ranjit Singh, the Sikh ruler of the Punjab region, who used the dethroned Sadozai prince, Shah Shujah Durrani, as his instrument. In 1834 Shah Shujah made a last attempt to recover his kingdom. He was defeated by Dost Mohammad Khan under the walls of Kandahar, but Ranjit Singh seized the opportunity to annex Peshawar. Dost Mohammad sent his son Akbar Khan to defeat the Sikhs at the Battle of Jamrud in 1837. The non- recovery of the Jamrud Fort became the Afghan Amir's worst concern.
At the intersection of British, Russian and, to a lesser degree, French imperial interests, political maneuvering was necessary. Rejecting overtures from Russia, he endeavoured to form an alliance with Great Britain, and welcomed Alexander Burnes to Kabul in 1837. Burnes, however, was unable to prevail on the governor-general, Lord Auckland, to respond to the emir's advances. Dost Mohammad was enjoined to abandon the attempt to recover Peshawar, and to place his foreign policy under British guidance. He replied by renewing his relations with Russia, and in 1838 Lord Auckland set the British troops in motion against him. To enable such an action, the British manufactured the evidence needed to justify the overthrow of the Afghan ruler.