In developing countries, invasive alien species (IAS) threaten smallholder farmer production and the food security of subsistence growers, but economic impacts are widely under-reported. Here, the economic impacts of IAS that threaten smallholder mixed maize farming in eastern Africa are presented. Maize is important for most smallholders and is commonly grown with horticultural crops and other cereals which collectively provide nutrition and income. These crops are also important for national economies. Estimates of the economic impacts of five major IAS: Chilo partellus, Maize Lethal Necrosis Disease, Parthenium hysterophorus, Liriomyza spp. and Tuta absoluta on mixed maize smallholders in six countries gave current combined annual losses of US$0.9–1.1 billion; and future annual losses (next 5–10 years) of US$1.0–1.2 billion. •Invasive alien species threaten smallholder production but economic impacts under-reported.•Economic impacts of 5 invasive alien species on smallholders in 6 African countries estimated.•Current annual economic losses from US$0.9 to 1.1 billion; near future losses US$1.0 to 1.2 billion.•Results confirm the growing threat to food security in the region.•Urgent need for coordinated response at regional, national and international levels.