After the succession by his son Humayun , the first Mughal Emperor, Babur, who ruled in India for a decade but was expelled. Eventually he took refuge with the Safavid shah of Persia, who helped him regain Delhi in 1555, the year before his death. Humayun's Persian wife, Hamida Begum, supervised the construction from 1562-1572 of her husband's tomb in Delhi.

The architect, Mirak Mirza Ghiyuath, was Persian and had previously designed buildings in Herat (now northwest Afghanistan), Bukhara (now Uzbekistan), and elsewhere in India.

The location chosen for the building on the bank of the Yamuna river adjoins the shrine of an important Sufi Chistiyya order saint, Nizam al-Din Awliya.

The Chistiyya was particularly venerated by the Mughals; Humayun's son, Akbar, would build his new palace at Fatehpur Sikri next to the shrine of another saint of the Chistiyya order.

The high rubble built enclosure is entered through two lofty double-storeyed gateways on the west and south. A Baradari (pavilion) occupies the centre of the eastern wall and a Hammam (bath chamber) in the centre of northern wall. The lofty mausoleum is in the centre of the enclosure and rises from a podium faced with series of cells having arched openings.

The central octagonal chamber contains the cenotaph, encompassed by octagonal chambers at the diagonals and arched lobbies on the side. Their openings are closed with perforated screens. Three arches dominate each side, the central one being the highest. This plan is repeated on the second storey too. The roof surmounted by a double dome (42.5m) of marble has pillared kiosks (Chhatris) placed around it. Several rulers of the Mughal dynasty lie buried here. Bahadur Shah Zafar had taken refuge in this tomb with three princes during the First War Independence (AD 1857).

On the southwestern side of the Humayun Tomb is located Barber's Tomb (Nai-ka-Gumbad), which stands on a raised platform, reached by seven steps from the south. The building is square on plan and consists of a signal compartment covered with a double-dome.