Since pre-Columbian times, Colombia has undergone transformation of large parts of its natural ecosystems, in particular in the Andean region. To date, little is known about the patterns and processes of this transformation and their relation with socioeconomic and biophysical aspects. Traditionally, the lack of integration of multidisciplinary data has hampered the possibility to understand complex phenomena like this. An integrated approach helps to bring into a relevant contextual analysis, data that are normally analyzed separately. This paper presents an approach to understanding ecosystem transformation by linking and integrating, spatially, data on ecosystem distribution and transformation, with demographic, land use, and settlement history data on a national scale. The transformation is analyzed and documented in order to explain the present situation and to make some general predictions about future tendencies. The results show that the demographic and transformation patterns follow clear historical trends that can be spatially differentiated, and are related to natural regions—plains and mountains, and altitude belts—and to general land uses. In particular, the patterns of the Andes and the lowlands show historically distinct tendencies. The Andean region has higher densities and transformation proportions than the lowlands. The older settlement areas show higher densities and more intensive land use, and tend to be strongly related to the Andean region.