The Paraguayan Pantanal is part of one of the largest freshwater wetlands in the world. It is also one of the richest ecosystems on the planet in terms of biodiversity. It is recognized as a RAMSAR site and on its way to being declared a UNESCO World Heritage Site, which faces various pressures mainly due to changes in land use. This study describes how these land use changes occurred over time in a place barely studied and thereby to lay the foundations for the decision-makers to undertake appropriate restoration and conservation measures. It aims to analyze the land cover dynamics in the Paraguayan Pantanal over 33 years, in the timeframe 1987–2020. A diachronic analysis of satellite images Landsat Collection 2 Level-2 was carried out. To process the different scenes into land cover maps, an unsupervised stacked classification process was conducted. In 33 years, 13,069.5 km2 (43.1%) of forest were intended to other uses, including herbaceous vegetation, grazing lands, aquatic vegetation, and water bodies. Between the periods 1987–2004, 2004–2020, and 1987–2020, there were 3014.4 km2 (9.9%), 5944.5 km2 (19.6%), and 9118.9 km2 (30.1%) of deforestation, considering the changes from forest to herbaceous vegetation and grazing lands. It is important to carry out a paradigm shift regarding the current mode of production, incorporating more sustainable livestock production techniques that allow the conservation of natural resources. Likewise, at the legislative level, land use regulations must be implemented and regulate the Forestry Law of Paraguay according to the current landscape situation.