William F. Albright has dated his reign to 715 BCE-687 BCE, while E. R. Thiele offers the dates 716 BCE-687 BCE.

The account of this king in the Hebrew Bible is contained in 2 Kings 18-20, Isaiah 36-39, and 2 Chronicles 29-32. These sources portray him as a great and good king, following the example of his great-grandfather Uzziah. He introduced religious reform, reinstated religious traditions. He set himself to abolish idolatry from his kingdom, and among other things which he did for this end, he destroyed the "brazen serpent," which had been relocated at Jerusalem, and had become an object of idolatrous worship. A great reformation was wrought in the kingdom of Judah in his day (2 Kings 18:4; 2 Chronicles 29:3-36). The author of 2 Kings ends his account of Hezekiah with praise (18:5).

Between the death of Sargon, and the succession of his son Sennacherib, Hezekiah sought to throw off his dependence to the Assyrian kings. He refused to pay the tribute enforced on his father, and "rebelled against the king of Assyria, and served him not," but entered into a league with Egypt (Isaiah 30; 31; 36:6-9). This led to the invasion of Judah by Sennacherib (2 Kings 18:13-16) in the 4th year of Sennacherib (701 BC). Hezekiah anticipated the Assyrian invasion, and made at least one major preparation: in an impressive engineering feat, a tunnel 533 meters long was dug in order to provide Jerusalem underground access to the waters of the Spring of Gihon, which lay outside the city. (The work is described in the Siloam Inscription, which has been dated to his reign on the basis of its script). At the same time, a wall was built around the Pool of Siloam, into which the waters from the spring flowed (Isaiah 22:11). An impressive vestige of this structure is the broad wall in the Jewish Quarter of the Old City of Jerusalem.

"When Hezekiah saw that Sennacherib had come, intent on making war against Jerusalem, he consulted with his officers and warriors about stopping the flow of the springs outside the city .. for otherwise, they thought, the King of Assyria would come and find water in abundance" (2 Chronicles 32:2-4). Sennacherib records on his monumental inscription, "The Prism of Sennacherib", how in his campaign against Hezekiah ("Ha-za-qi-(i)a-ú") he took 46 cities in this campaign (column 3, line 19 of Taylor prism), and besieged Jerusalem ("Ur-sa-li-im-mu") with earthworks. Eventually Hezekiah saw Sennacherib's determination, and offered to pay him three hundred talents of silver and thirty of gold in tribute, despoiling the Temple to produce the promised amount (18:14-16) (see also Biblical and Talmudic units of measurement).

The narrative in the Bible states Sennacherib invaded Judah (Isaiah 33:1; 2 Kings 18:17; 2 Chronicles 32:9; Isaiah 36) and besieged Jerusalem. According to the Biblical accounts, this invasion ended in the destruction of Sennacherib's army, when Hezekiah prayed to God and "that night the angel of the Lord went out, and smote in the camp of the Assyrians 185,000 men." The author of the Books of Kings remembers to include the fact that (19:37), seventeen years later, Sennacherib was assassinated by his sons Adrammelech and Sharezer, and Esarhaddon became the Assyrian king. There is also a less miraculous account from the Assyrian side, that Sennacherib raised his siege of Jerusalem after Hezekiah acknowledged Sennacherib as his overlord and paid him tribute.

The narrative of Hezekiah's sickness and miraculous recovery is found in 2 Kings 20:1, 2 Chronicles 32:24, Isaiah 38:1. Various ambassadors came to congratulate him on his recovery, among them Merodach-baladan, the king of Babylon (2 Chronicles 32:23; 2 Kings 20:12).