Solar photocatalytic inactivation (SPCI) of E. coli as the indicator microorganism using LaFeO3 (LF) has already been investigated under various experimental conditions, excluding any role of natural organic matter (NOM). However, comprehensive information about the behavior of E. coli and its inactivation mechanism in the presence of NOM, as well as the behavior of NOM components via solar photocatalysis using LF as a photocatalyst, has prime importance in understanding real natural water environments. Therefore, in this study, further assessment was devoted to explore the influence of various NOM representatives on the SPCI of E. coli by using LF as a novel non-TiO2 photocatalyst. The influence of NOM as well as its sub-components, such as humic acids (HA) and fulvic acids (FA), was also investigated to understand different NOM-related constituents of real natural water conditions. In addition to spectroscopic and mechanistic investigations of cell-derived organics, excitation emission matrix (EEM) fluorescence spectra with parallel factor multiway analysis (PARAFAC) modeling revealed further information about the occurrence and/or disappearance of NOM-related and bacteria-related fluorophores upon LF SPCI. Both the kinetics as well as the mechanism of the LF SPCI of E. coli in the presence of NOM compounds displayed substrate-specific variations under all conditions.