Crustose coralline algae (CCA), a group of calcifying red algae found commonly in benthic marine ecosystems worldwide, perform essential ecological functions on coral reefs, including creating benthic substrate, stabilizing the reef structure and inducing coral settlement. An important feature of CCA is the ability to keep their surfaces free of epiphytic algae, thereby reducing algal overgrowth and allowing them access to light. However, the mechanisms by which CCA prevent settlement of opportunistic seaweeds (fleshy macroalgae) are not fully understood, nor is whether these mechanisms vary among CCA species. In our study based on the Great Barrier Reef, we demonstrate that three common CCA species (Titanoderma pustulatum, Porolithon onkodes and Neogoniolithon sp.) have a remarkable ability to deter settlement of seaweed spores. We provide experimental evidence that the CCA use allelopathy and microbial inhibition against the settlement of spores of the brown seaweed Padina boergesenii. Methanol extracts of allelopathic compounds from T. pustulatum, Po. onkodes and Neogoniolithon sp. significantly reduced the settlement of Pa. boergesenii spores by 4.3 times, 3.0 and 3.8 times, respectively. Further, we found that microbial biofilms, while having a lower inhibitory effect than allelopathic compounds, also reduced seaweed settlement of Pa. boergesenii. Our study demonstrates that allelopathy and microbial inhibition, in addition to epithallial tissue sloughing, are mechanisms employed by CCA to prevent the settlement of epiphytic algae. Understanding the mechanisms by which CCA avoid seaweed overgrowth contributes to our understanding of the dynamics of seaweed proliferations on reefs and to the ecological knowledge of this important group of reefbuilding organisms.