Quiriguá's history parallels that of Copán, of which it was a dependency during much of the Classic period. Of the three sites in this area, only the present archaeological park is of interest.

Quiriguá's location lent itself to the carving of giant stelae. Beds of brown sandstone in the nearby Río Motagua had cleavage planes suitable for cutting large pieces. Though soft when first cut, the sandstone dried hard in the air. With Copán's expert artisans nearby for guidance, Quiriguá's stone carvers were ready for greatness. All they needed was a great leader to inspire them – and to pay for the carving of the huge stelae.

That leader was K'ak' Tiliw Chan Yo'at (Cauac Sky; r 725–84), who decided that Quiriguá should no longer be under the control of Copán. In a war with his former suzerain, Cauac Sky took Uaxaclahun Ubak K’awil (King 18 Rabbit) of Copán prisoner in 737 and later had him beheaded. Independent at last, Cauac Sky commissioned his stonecutters to go to work, and for the next 38 years they turned out giant stelae and zoomorphs dedicated to his glory.

Cauac Sky's son Sky Xul (r 784–800) lost his throne to a usurper, Jade Sky. This last great king of Quiriguá continued the building boom initiated by Cauac Sky, reconstructing Quiriguá's Acrópolis on a grander scale.

Quiriguá remained unknown to Europeans until the explorer and diplomat John L Stephens arrived in 1840. Impressed by its great monuments, Stephens lamented the world's lack of interest in them in his book Incidents of Travel in Central America, Chiapas and Yucatan (1841).

Stephens tried to buy the ruined city in order to have its stelae shipped to New York, but the owner, Señor Payes, assumed that Stephens (being a diplomat), was negotiating on behalf of the US government and that the government would pay. Payes quoted an extravagant price, and the deal was never made.

Between 1881 and 1894, excavations were carried out by Alfred P Maudslay. In the early 20th century all the land around Quiriguá was sold to the US-based United Fruit Company and turned into banana groves. The company is gone, but the bananas and Quiriguá remain. Restoration of the site was carried out by the University of Pennsylvania in the 1930s. In 1981 Unesco declared the ruins a World Heritage Site, one of only three in Guatemala (the others are Tikal and Antigua).