Macroinvertebrate organisms were sampled at four sites on Tecate Creek (U.S.–Mexico) and quantitatively evaluated using the SIGNAL-w (Stream Invertebrate Grade Number—Average Level-weighted) index. A morphological assessment of the stream structure was also carried out. Bioindication by SIGNAL reflected a very low water quality in the upper three sampled stream reaches, but with a significant improvement by the last site on the Rio Alamar, but only to a grade of critical to high pollution over a flowing distance of 29 km. Levels of BOD and ammonium-N at the Rio Alamar (Toll Bridge) site remained quite high, 56 mg/L and 48 mg/L, respectively. Metal levels also generally decreased as the water flowed downstream to the the Rio Alamar. Despite the fact that Tecate Creek has a quite natural morphological structure, solid inorganic surfaces and aquatic macrophytes (as settlement area) are mostly absent in Tecate Creek. This lack of stable habitats prevents the development of an effective biofilm which would significantly enhance self-purification.