Cuatro Cienegas is a natural geopark that exhibits a vast reservoir of geological, geochemical and geobiological diversity, including shallow‐water microbial carbonates with clotted micrite textures known as thrombolites. Thrombolites mainly occur as domes and massive irregular carbonates along the margins of Rio Mezquites in Cuatro Cienegas, northern Mexico. Because their clotted textures result from diverse abiotic and biotic interactions at the microbial–mineral interface, the formation of clots in thrombolites continues to be a contentious issue. Through a petrographic, scanning electron microscopy and bulk biogeochemical analysis, this study investigated the role of endolithic cyanobacteria in the generation of thrombolitic clots. Their microclotted fabric is characterized by 50 to 200 μm peloidal clots, pores, fenestrae, crevices and cavities as main components. Thrombolites also contain microbial microstructures, some of them interpreted as the endolithic contribution to the genesis of clotted micrite. Thrombolites and associated fresh microbial mats are composed of cyanobacteria, green algae and diatoms. Petrography and cast‐embedded scanning electron microscopy micrographs also show the presence of filamentous endolithic cyanobacteria inside the thrombolitic framestone. The geochemical bulk characterization for carbon and oxygen isotopes shows average values of −0.7‰ Vienna PeeDee Belemnite and −8.0‰ Vienna PeeDee Belemnite, respectively. The organic matter preserved in their mineral matrix and associated microbial mats indicated the putative presence of cyanobacterial hopanoids. The high diversity of peloids and the microboring evidence, together with observed microstructures, suggest that clots may also form by the concurrent precipitation and dissolution of the thrombolites. Among the known sources of peloidal clots, microbial boring may be an additional micrite source for clot formation. Microbial carbonate dissolution may also promote heterogenous lithification by hydration and dehydration cycles. Thrombolites reflect complex systems due to concurrent interactions among producers (phototrophs), consumers (small invertebrates), mineralization (carbonate precipitation induced by phototrophs) and endolithic dissolution. The microstructures inside thrombolites, in conjunction with biogeochemical attributes of bulk thrombolites, may provide unambiguous sedimentary biosignatures.