This paper investigates the impact of human activity and mobility (HAM) in the spreading dynamics of an epidemic. Specifically, it explores the interconnections between HAM and its effect on the early spread of the COVID-19 virus. During the early stages of the pandemic, effective reproduction numbers exhibited a high correlation with human mobility patterns, leading to a hypothesis that the HAM system can be studied as a coupled system with disease spread dynamics. This study applies the generalized Koopman framework with control inputs to determine the nonlinear disease spread dynamics and the input–output characteristics as a locally linear controlled dynamical system. The approach solely relies on the snapshots of spatiotemporal data and does not require any knowledge of the system’s underlying physical laws. We exploit the Koopman operator framework by utilizing the Hankel dynamic mode decomposition with Control (HDMDc) algorithm to obtain a linear disease spread model incorporating human mobility as a control input. The study demonstrated that the proposed methodology could capture the impact of local mobility on the early dynamics of the ongoing global pandemic. The obtained locally linear model can accurately forecast the number of new infections for various prediction windows ranging from two to four weeks. The study corroborates a leader-follower relationship between mobility and disease spread dynamics. In addition, the effect of delay embedding in the HDMDc algorithm is also investigated and reported. A case study was performed using COVID infection data from Florida, US, and HAM data extracted from Google community mobility data report.