Background: The lack of empirical data on the malaria status of orphans and vulnerable children (OVC), access to long-lasting insecticide-treated nets (LLINs), and knowledge about the disease can hamper the development of effective policies and programs to address their malaria-related needs. Aim: The aim of this study was to evaluate knowledge of malaria transmission and utilization of LLINs among OVC in Ondo metropolis, Nigeria. Materials and Methods: A cross-sectional study was conducted in Ondo City, Ondo State, Nigeria, between January and March 2018. The study was carried out among 66 OVC (age 5–19 years) using questionnaires. Information on socio-demography, LLIN utilization, knowledge and risks of malaria transmission among OVC was sought. Results: The use of LLINs (80.9%) among OVC was significantly higher than the use of insecticide spray (6.1%) and mosquito coils (12.1%) (p <0.0001). Knowledge about malaria transmission was relatively high, and the majority of children (60.6%) believed malaria is mostly transmitted during the dry season. Fewer children (21.2%) had a history of malaria in the last 3 months. Conclusions: The risk of malaria transmission was low among OVC. Continuous accessibility of orphanage homes to LLINs should be sustained to prevent malaria transmission among OVC.