To contribute to a more comprehensive understanding of human wayfinding behaviors in complex buildings, we propose a framework that incorporates the impact of critical factors from both the environment and humans. The influence of the environment is summarized through the concept of environmental legibility (EL), an integration of different space syntax methods that addresses visibility, connectivity, and layout complexity of buildings. Human factors are assessed through psychometric tests, self-ratings for sense of direction, and a report of familiarity. To test this framework, we conducted behavioral experiments involving 24 novices and 28 experts. Three different processes of wayfinding—wayfinding performance, acquisition of spatial knowledge, and development of spatial awareness—were measured and evaluated. Results show that EL and individual differences impact all three processes. There is a predominant impact of EL on wayfinding performance and the development of spatial awareness. Not surprisingly, familiarity has a predominant impact on the acquisition of spatial knowledge.