The main population centres in El Progreso are Guastatoya, Sanarate and San Agustín Acasaguastlán.

Historically, the area now included in the department of El Progreso was known as Guastatoya or Huastatoya, derived from Nahuatl huäxyötl or huäxin ("calabash") and atoyac ("last"), meaning the last place that calabashes grow, a reference to the change in altitude that occurs in the department, and corresponding climatic change from cold to hot.

[2] The Spanish colonial corregimiento of San Cristóbal Acasaguastlán was established in 1551 with its seat in the town of that name, in what is now the eastern portion of the modern department.

[4] Acasaguastlán was one of few pre-conquest centres of population in the middle Motagua River drainage, due to the arid climate.

[3] In the 1520s, immediately after conquest, the inhabitants paid taxes to the Spanish Crown in the form of cacao, textiles, gold, silver and slaves.

[6] The region was subject to a strong influx of Spanish colonists due to its location on the route between the colonial capital and the Caribbean Sea, and hence to Spain, resulting in the hispanicisation of the territory.

For a short time from December 1919 to June of the following year, the department was renamed Estrada Cabrera at the request of its constituent municipalities, in order to honour the then-president.

[10] The departmental capital of Guastatoya was badly affected by the 1976 Guatemala earthquake, which completely destroyed all historic architecture in the town.

[4] The highest point in the department is Cerro El Pinalón, in the Sierra de las Minas, at 2,962 metres (9,718 ft).

[15] In 2013, 930 deaths were registered in the department, demonstrating a 3.5% drop on the previous year, and 1.3% of the national total:[16] Agricultural products include coffee, sugar cane, tobacco, maize, beans, cacao, annatto, tomatoes, vanilla, cotton, and a variety of other fruits.

[4] Local craft production includes basketwork, ropemaking, leatherwork, items fashioned from palm, and tulle netting.

[4] Local tourist attractions include thermal baths near Sanarate and San Antonio La Paz.