Systemic fungal infections by filamentous fungi, particularly in the immunocompromised population, represent a serious threat to public health. The increase of resistant strains to classic antifungal drugs, especially azoles, is a global health problem and some infections become almost impossible to treat. Furthermore, the emergence of new multidrug-resistant fungal species, such as Scedosporium spp. and Fusarium spp., as etiological agents, pose a challenge in the treatment. On the other hand, superficial fungal infections by dermatophytes have a high incidence affecting around 20 to 30% of the healthy human population. Therefore, the discovery and development of new antifungal compounds with a broad-spectrum and able to modulating and/or eradicating antifungal resistance have become an essential and urgent strategy. Taking into account that thioxanthones are privileged structures and bioisosteres of xanthones, three thioxanthones were synthesized and, subsequently, their activity as potential agents against filamentous fungi were evaluated. Minimum inhibitory concentration and minimum lethal concentration was tested against clinically relevant species, using the broth microdilution method. The derivatives were synthesized through aromatic nucleophilic substitution reactions, using a chlorinated thioxanthone and a primary amine as building blocks, and showed interesting results against most of the isolates tested, including strains intrinsically resistant or that acquired resistance to fluconazole or other azoles; among the tested compounds, one of the thioxanthone showed more promising activity. These findings highlight the potential value of the thioxanthone derivatives as new models for antifungal agents for the treatment of systemic and superficial fungal infections.