The play opens in Persepolis. The Persian emperor, Mycetes, dispatches troops to dispose of Tamburlaine, a Scythian shepherd and at that point a nomadic bandit. In the same scene, Mycetes' brother Cosroe plots to overthrow Mycetes and assume the throne.
The scene shifts to Scythia, where Tamburlaine is shown wooing, capturing, and winning Zenocrate, the daughter of the Egyptian king. Confronted by Mycetes' soldiers, he persuades first the soldiers and then Cosroe to join him in a fight against Mycetes. Although he promises Cosroe the Persian throne, Tamburlaine reneges on this promise and, after defeating Mycetes, takes personal control of the Persian Empire.
Suddenly a powerful figure, Tamburlaine decides to pursue further conquests. A campaign against Turkey yields him the Turkish king Bajazeth and his wife Zabina as captives; he keeps them in a cage and at one point uses Bajazeth as a footstool.
After conquering Africa and naming himself emperor of that continent, Tamburlaine sets his eyes on Damascus; this target places the Egyptian Sultan, his father-in-law, directly in his path. Zenocrate pleads with her husband to spare her father. He complies, instead making the Sultan a tributary king. The play ends with the wedding of Zenocrate and Tamburlaine, and the crowning of the former as Empress of Persia.
In Part 2, Tamburlaine grooms his sons to be conquerors in his wake as he continues to conquer his neighbouring kingdoms. One of his sons, Calyphas, preferring to stay by his mother's side and not risk death, incurs Tamburlaine's wrath. Seeing this son as a coward, Tamburlaine kills him in anger after a battle in which he refuses to fight. During this time, Bajazeth's son, Callapine, plans to avenge his father's death. Finally, while attacking an Islamic nation, he scornfully burns a copy of the Qur'an and claims to be greater than God. Suddenly, Tamburlaine is struck ill and dies, giving his power to his remaining sons, but still aspiring to greatness as he departs life.