Aims To evaluate the phytotoxic, antifungal and antioomycete activity; and, determine the chemical composition of the volatile organic compounds (VOCs) and semi‐volatile metabolites produced by the endophyte Hypoxylon anthochroum strain Blaci isolated from Bursera lancifolia. Methods and Results Based on its macro‐ and micro‐morphological features, the strain Blaci was identified as Nodulisporium sp.; partial analysis of its ITS1‐5.8‐ITS2 ribosomal gene sequence revealed the identity of the teleomorphic stage of the fungus as H. anthochroum. Phytotoxic and antimicrobial activities of VOCs, and culture medium and mycelium organic extracts from H. anthochroum Blaci were determined by simple and multiple antagonism bioassays, and gas phase and agar dilution bioassays respectively. The volatile and semi‐volatile metabolites were identified by gas chromatography–mass spectrometry. VOCs from a 5‐day H. anthochroum strain Blaci culture caused the inhibition of seed germination, root elongation and seedling respiration on Amaranthus hypochondriacus, Panicum miliaceum, Trifolium pratense and Medicago sativa. In addition, extracts, phenylethyl alcohol and eucalyptol main compounds present in the VOCs and extract displayed a high phytotoxic activity, inhibiting the three physiological processes on the four test plants in a concentration‐dependent manner. Conclusions The results revealed that H. anthochroum strain Blaci produces a mixture of VOCs. These VOCs showed a strong phytotoxic activity on seed germination, root elongation, and seedling respiration of four plants and slightly affected the growth of phytopathogenic fungi and oomycetes. Also, the culture medium and mycelium extracts of H. anthochroum showed a high phytotoxic activity on the four test plants and, generally, the culture medium extract was more phytotoxic than the mycelium extracts. Significance and Impact of the Study This work firstly reports the phytotoxic activity of volatile and semi‐volatile compounds produced by the endophyte H. anthochroum strain Blaci on seed germination, root elongation, and seedling respiration of four different plants; consequently, these compounds could be useful in biocontrol of weeds and plant pathogens.