He came to the throne aged ten in 1524 and came under the control of the Qizilbash who formed the backbone of the Safavid Empire. The Qizilbash leaders fought among themselves for the right to be regents over Tahmasp, and by doing so held most of the effective power in hands in the empire. Upon adulthood, however, Tahmasp was able to reassert the power of the Shah and control the tribesmen with the start of the introduction of large amounts of Caucasian elements, effectively and purposefully creating a new layer in Iranian society, solely composed of ethnic Caucasians. This new layer, also called the third force in some of the modern day sources, would be solely composed of hundreds of thousands of ethnic Circassians, Georgians and Armenians, and they would continue to play a crucial role in Persia's royal household, harems, civil and military administration, as well as in all other thinkable and available positions for centuries after Tahmasp, and they would eventually fully eliminate the effective power of the Qizilbash in most of the functioning posts of the empire, by which they would also become the most dominant class in the meritocratic Safavid kingdom as well. One of his most notable successors, the greatest Safavid emperor, Abbas I (also known as Abbas the Great) would fully implement and finalize this policy and the creation of this new layer in Iranian society.
Tahmasp's reign was marked by foreign threats, primarily from the Safavid's arch rival, the Ottomans, and the Uzbeks in the far east. In 1555, however, he regularized relations with the Ottoman Empire through the Peace of Amasya. By this treaty historical Armenia and Georgia were divided equally between the two, the Ottoman Empire obtained most of Iraq, including Baghdad, which gave them access to the Persian Gulf, while the Persians retained their former capital Tabriz and all their other north-western territories in the Caucasus (Dagestan, Azerbaijan) and as they were prior to the wars. The frontier thus established ran across the mountains dividing eastern and western Georgia (under native vassal princes), through Armenia, and via the western slopes of the Zagros down to the Persian Gulf. The Ottomans, further, gave permission for Persian pilgrims to go to the holy places of Mecca and Medina as well as to the Shia sites of pilgrimages in Iraq. This peace lasted for 30 years, until it was broken in the time of Shah Mohammad Khodabanda.
Tahmasp is also known for the reception he gave to the fugitive Mughal Emperor Humayun as well as Suleiman the Magnificent's son Bayezid, which is depicted in a painting on the walls of the Safavid palace of Chehel Sotoon.
One of Shah Tahmasp's more lasting achievements was his encouragement of the Persian rug industry on a national scale, possibly a response to the economic effects of the interruption of the Silk Road carrying trade during the Ottoman wars.
Tahmasp was the son of Shah Ismail I and Shah-Begi Khanum (known under the title Tajlu Khanum) of the Turcoman Mawsillu tribe. He was only 10 years old when he succeeded his father Shah Ismail, the founder of Safavid rule in Iran. Too young to rule in his own right, Tahmasp came under the control of the Qizilbash. Some of the tribes recognised a Qizilbash leader, Div Sultan Rumlu, as regent (atabeg) to the shah, but others dissented and in 1526 a bloody civil war broke out among the differing factions. Div Sultan emerged victorious but his ally, Chuha Sultan Takkalu, turned against him and urged the shah to get rid of him. On 5 July 1527 as Div Sultan arrived for a meeting of the government, Tahmasp shot an arrow at him. When it failed to kill him, the shah's supporters finished him off.