Due to the public health risks of wastewater contamination of coastal waters worldwide, there is a need for rapid tracking of sewage-laden flows. Fluorescence-based submersible sensors have been used for monitoring organic contaminants in natural waters; however, their potential to serve as a real-time warning of high bacteria concentrations and wastewater pollution under estuarine conditions with tidal influence remains to be evaluated. The Tijuana River Estuary has been plagued by decades of cross-border sewage flow that poses major public health risks for beach goers, Navy Seals, and border patrol agents, and has resulted in long-term beach closures on both sides of the US-Mexico border. This study assessed the use of submersible, in-situ tryptophan-like (TRP) and humic-like (CDOM) fluorescence sensors for tracking fecal indicator bacteria (FIB) concentrations in real-time in the Tijuana River Estuary during three conditions: 1) dry weather without cross-border sewage flow, 2) dry weather with cross-border flow, and 3) wet weather with cross-border flow. FIB concentrations of samples collected during scenario #2, dry weather with cross-border flow, were most significantly correlated with submersible TRP and CDOM sensor fluorescence. TRP and CDOM fluorescence were also measured using a benchtop, scanning fluorometer with instrument corrections, which yielded significant correlation (p < 0.001) with FIB concentrations under all hydrologic conditions, reflecting the superior performance of the benchtop instrument. Regular maintenance conducted weekly or fortnightly was required to minimize sensor fouling. Also, the presence of high strength wastewater resulted in an inner filter effect, which requires post-processing corrections or data flagging as part of quality control efforts. Overall, we conclude that TRP and CDOM sensors are currently able to provide real-time warning of sewage contamination. However, quantifying the magnitude of contamination is not yet possible in real-time, and efforts are underway in our research groups to achieve this goal.