Perception of odors created by volatile molecules is central for human wellbeing. The chemistry of volatile compounds is especially important inside the built environment as humans spend increasingly greater time indoors. Beside unpleasant smells, exposure to airborne contaminants can directly impact our health. However, the comprehensive understanding of the composition and behavior of the indoor volatile and semi-volatile compounds (volatilome) is limited, in part due to the tremendous complexity and fleeting nature of these chemical distributions. This study explored the comprehensive volatilome, as opposed to individual compounds, of the indoor environment of a residence. For the first time, we mapped a spatial distribution of volatiles within a house as well as traced temporal volatilome changes. The impact of occupants’ activities over a month period were assessed in relation to the observed indoor volatile chemistry and changes in global chemical distributions across time. Each indoor activity generated a trail of volatiles, and the indoor volatilome after human habitation was found to be distinctly reshaped. Using molecular networking, we explored how multiple chemical families were affected. The portion of volatilome that has accumulated due to human occupancy appears to be more harmful to human health than emissions from the built environment itself. This is an important consideration for any other human environment with accumulated volatile chemistry, such as hospitals or office spaces.