Purpose: The accessibility of a certain place can evolve either as the direct result of transport changes or as a consequence of the spatial redistribution of economic activities. These two factors are often indistinguishable—especially at regional level—since improved infrastructure stimulates relocation of activities. Moreover, infrastructure investment choices tend to follow population and economic activity patterns, distorting the cause and effect relationship between infrastructure and accessibility even further. The methodology and results presented here decompose the impact of both factors in terms of accessibility using Spanish data between 1960 and 2010. During this period, Spain experienced profound changes in transport infrastructure and economic activity. Methods: We use the potential accessibility indicator and resort to index number theory to disentangle the contribution of transport infrastructure from that of land-use changes. Detailed historical data on road infrastructure and population is used to represent the transport and land-use components of accessibility. Results: Our results show that changes in transport infrastructure had a relevant impact on accessibility, as expected, but changes in the spatial distribution of population had an even greater effect. This outcome may be used as an argument for sustainable accessibility, a concept that advocates integration of transport and land use planning.