Orphaned at an early age, he was raised in the city of Herāt (Herāt school) by the painter Mīrak Naqqāsh, who enjoyed the patronage of the Timurid princes who ruled the city. Behzād studied under his guardian and in 1486 became head of the Herāt academy, a post he held until 1506. Under his direction the academy became a greater centre of art than ever.

In 1506 Shāh Esmāʿīl I, founder of Iran's Ṣafavid dynasty, conquered the city. In 1514 Esmāʿīl's son Ṭahmāsp was made governor of Herāt, and, when he returned to Tabrīz (Tabrīz school) in 1522, Behzād returned in his train. At Tabrīz he continued to enjoy royal patronage and was named director of the royal library and placed in charge of the production of the elaborate illuminated and illustrated manuscripts. He held the post until his death.

Both as a teacher and painter Behzād was a leading force in the development of Tabrīz as a centre of art. His students included the painters Qāsim ʿAlī, Mīr Sayyid ʿAlī (Mīr Sayyid ʿAli), Āqā Mīrak, and Muẓaffar ʿAlī.

A major problem in assessing Behzād's work precisely is the difficulty in identifying specific works as coming from his hand. His pupils worked closely to imitate his style. In addition, he became the standard of excellence in his own age, and collectors of the time would identify works of excellence as being by Behzād with little or no supporting evidence. Behzād signed few of his paintings, and only 32 have been definitively attributed to him, all executed between 1486 and 1495.

While Behzād's work represents no radical departure from earlier styles, his technical skill, combined with his originality in composition and dramatic presentations and his superb knowledge of colour, made him the master painter of his time. In a style marked by harmony, humanism, and grace, he was able to free the miniature from stiffness in presentation and excessive concern with detail. Behzād injected new energy and realism into Persian painting.

Two of his earliest surviving works are signed illustrations for a manuscript of the Persian poet Saʿdī's classic Golestān (“The Rose Garden”). Five miniatures he contributed to a manuscript of Saʿdī's Būstān, copied in 1488 and now preserved in the Egyptian National Library at Cairo, are considered by many scholars to be the best surviving examples of his work. His painting of the building of the castle of Khawarnaq, done about 1494, clearly shows Behzād's ability to portray vividly a complex scene in a rich and fluid composition. The work shows careful observation and an ability to display significant detail while stripping away unimportant clutter.