| Date | Event | Modern department |
| – March 1524 | Spanish defeat the K'iche' | Retalhuleu, Suchitepéquez, Quetzaltenango, Totonicapán and El Quiché |
| 8 February 1524 | Battle of Zapotitlán, Spanish victory over the K'iche' | Suchitepéquez |
| 12 February 1524 | First battle of Quetzaltenango results in the death of the K'iche' lord Tecun Uman | Quetzaltenango |
| 18 February 1524 | Second battle of Quetzaltenango | Quetzaltenango |
| Spanish under Pedro de Alvarado raze Q'umarkaj, capital of the K'iche' | El Quiché |
| 14 April 1524 | Spanish enter Iximche and ally themselves with the Kaqchikel | Chimaltenango |
| 18 April 1524 | Spanish defeat the Tz'utujil in battle on the shores of Lake Atitlán | Sololá |
| 9 May 1524 | Pedro de Alvarado defeats the Pipil of Panacal or Panacaltepeque near Izcuintepeque | Escuintla |
| 26 May 1524 | Pedro de Alvarado defeats the Xinca of Atiquipaque | Santa Rosa |
| 27 July 1524 | Iximche declared first colonial capital of Guatemala | Chimaltenango |
| 28 August 1524 | Kaqchikel abandon Iximche and break alliance | Chimaltenango |
| 7 September 1524 | Spanish declare war on the Kaqchikel | Chimaltenango |
| The Poqomam capital falls to Pedro de Alvarado | Guatemala |
| 13 March 1525 | Hernán Cortés arrives at Lake Petén Itzá | Petén |
| Zaculeu, capital of the Mam, surrenders to Gonzalo de Alvarado y Contreras after a lengthy siege | Huehuetenango |
| Chajoma rebel against the Spanish | Guatemala |
| Acasaguastlán given in encomienda to Diego Salvatierra | El Progreso |
| Spanish captains sent by Alvarado conquer Chiquimula | Chiquimula |
| 9 February 1526 | Spanish deserters burn Iximche | Chimaltenango |
| Spanish abandon their capital at Tecpán Guatemala | Chimaltenango |
| San Mateo Ixtatán given in encomienda to Gonzalo de Ovalle | Huehuetenango |
| Spanish routed at Uspantán | El Quiché |
| Rebellion in Chiquimula put down | Chiquimula |
| 9 May 1530 | Kaqchikel surrender to the Spanish | Sacatepéquez |
| Ixil and Uspantek surrender to the Spanish | El Quiché |
| Juan de León y Cardona founds San Marcos and San Pedro Sacatepéquez | San Marcos |
| Foundation of Cobán | Alta Verapaz |
| First reductions of the Chuj and Q'anjob'al | Huehuetenango |
| Corregimiento of San Cristóbal Acasaguastlán established | El Progreso, Zacapa and Baja Verapaz |
| Lowland Maya kill Francisco de Vico | Alta Verapaz |
| Reduction of Topiltepeque and Lakandon Ch'ol | Alta Verapaz |
| Franciscan missionaries arrive at Nojpetén, capital of the Itzá | Petén |
| Further missionary expeditions to Nojpetén | Petén |
| Reduction of San Mateo Ixtatán and Santa Eulalia | Huehuetenango |
| 29 January 1686 | Melchor Rodríguez Mazariegos leaves Huehuetenango, leading an expedition against the Lacandón | Huehuetenango |
| Franciscan friar Andrés de Avendaño attempts to convert the Itzá | Petén |
| 28 February 1695 | Spanish expeditions leave simultaneously from Cobán, San Mateo Ixtatán and Ocosingo against the Lacandón | Alta Verapaz, Huehuetenango and Chiapas |
| Andrés de Avendaño forced to flee Nojpetén | Petén |
| 13 March 1697 | Nojpetén falls to the Spanish after a fierce battle | Petén |