In ancient times Megiddo was an important city-state. It is also known alternatively as Tel Megiddo (Hebrew) and Tell al-Mutesellim (Arabic). Megiddo is a tel (hill or mound) made of 26 layers of the ruins of ancient cities in a strategic location at the head of a pass through the Carmel Ridge, which overlooks the Valley of Jezreel from the west. The name Armageddon mentioned in the New Testament derives from Har Megiddo (Hebrew) meaning Mount of Megiddo.

Megiddo was a site of great importance in the ancient world, as it guarded the western branch of a narrow pass and an ancient trade route which connected the lands of Egypt and Assyria. Because of its strategic location at the crossroads of several major routes, Megiddo and its environs have witnessed several major battles throughout history. The site was inhabited from approximately 7000 BC to 586 BC (the same time as the destruction of the First Israelite Temple in Jerusalem by the Babylonians, and subsequent fall of Israelite rule and exile). One of its claims to importance is the fact that since this time it has remained uninhabited, thereby preserving the ruins of its time periods pre-dating 586 BC without newer settlements disturbing them.

Megiddo is mentioned in Ancient Egyptian writings because one of Egypt's mighty kings, Thutmose III, waged war upon the city in 1478 BC. The battle is described in detail in the hieroglyphics found on the walls of his temple in Upper Egypt. Named in the Bible Derekh HaYam (Hebrew: דרך הים‎), or "Way of the Sea," it became an important military artery of the Roman Empire and was known as the Via Maris.

Modern Kibbutz of Megiddo is nearby just a little less than 1 kilometre (0.62 mi) away to the south.

Today, Megiddo is an important junction on the main road connecting the center of Israel with lower Galilee and the northern region. Therefore, to this day it remains a site of strategic importance as it lies at the northern entrance to Wadi Ara, an important mountain pass connecting the Jezreel Valley with Israel's coastal plain.

Megiddo has been the site of numerous battles throughout history, with the site changing hands many times. Three of the more famous battles include:

The Book of Revelation mentions apocalyptic military amassment at Armageddon, a name derived from Megiddo. The word has become a byword for the end of the age.

Megiddo has been excavated three times and is currently being excavated yet again. The first excavations were carried out between 1903 and 1905 by Gottlieb Schumacher for the German Society for the Study of Palestine. Techniques used were rudimentary by later standards and Schumacher's field notes and records were destroyed in World War I before being published. After the war, Carl Watzinger published the remaining available data from the dig.

In 1925, digging was resumed by the Oriental Institute of the University of Chicago, financed by John D. Rockefeller, Jr., continuing until the outbreak of the Second World War. The work was led initially by Clarence Fisher, and later by P. L. O. Guy, Robert Lamon, and Gordon Loud. During these excavations it was discovered that there were around 8 levels of habitation, and many of the uncovered remains are preserved at the Rockefeller Museum in Jerusalem and the Oriental Institute of Chicago.

Yigael Yadin conducted excavations in 1960, 1966, 1967, and 1971 for the Hebrew University. The formal results of those digs have not yet been published, though in 2005 a grant was issued by the Shelby White - Leon Levy Program for Archaeological Publications to produce an expedition final report.