The use of plant secondary metabolites is an attractive strategy to control weeds. In this work, cypress (Cupressus leylandii) leaves were collected and tested as aqueous macerates or mulches for their ability to control seed germination and seedling growth of Trifolium repens and Lepidium sativum. Leaves were collected on trees facing the north (S) or facing the sun (L). The rate of seed germination measured on sand was drastically slowed down by the cypress leaves after 8 d of maceration, reaching inhibition of >85% compared to the control at 7 d post-imbibition (dpi). Analysis of macerates by UHPLC-MS revealed the presence of organic acids, phenols, and sugars in amounts increasing with maceration time and the phytotoxic effect. A 5 cm layer of cypress leaf mulch also significantly reduced (p < 0.001) the rate of seedling appearance of Lepidium sativum measured on potting soil compared to the control. Mulches prepared using L leaves were more efficient than those prepared with S leaves (p = 0.0029). Analysis of ethanolic extracts of leaves by mass spectrometry (MS) coupled to liquid (UHPLC) or gas chromatography (GC) showed the presence of a variety of monoterpenes, monoterpenoids, and diterpenoids with a labdane backbone. They were all more concentrated in mulches prepared with L leaves than those prepared with S leaves, in particular diterpenoids, which were about 10-fold more concentrated. However, the identification of phytotoxic components needs further research. It is concluded that due to their phytotoxic properties, Cupressus leylandii leaves could be used as mulch or macerate for target treatment of weedy areas.