During the course of screening Ethiopian medicinal plants for their antimalarial properties, it was found that the dichloromethane extract of the roots of Kniphofia foliosa Hochst. (Asphodelaceae), which have long been used in the traditional medicine of Ethiopia for the treatment of abdominal cramps and wound healing, displayed strong in vitro antiplasmodial activity against the chloroquine‐sensitive 3D7 strain of Plasmodium falciparum with an ED50 value of 3.8 µg/mL and weak cytotoxic activity against KB cells with an ED50 value of 35.2 µg/mL. Five compounds were isolated from the roots and evaluated for their in vitro antimalarial activity. Among the compounds tested, 10‐(chrysophanol‐7′‐yl)‐10‐(ξ )‐hydroxychrysopanol‐9‐anthrone and chryslandicin, showed a high inhibition of the growth of the malaria parasite, P. falciparum with ED50 values of 0.260 and 0.537 µg/mL, respectively, while the naphthalene derivative, 2‐acetyl‐1‐hydroxy‐8‐methoxy‐3‐methylnaphthalene, exhibited a less significant antimalarial activity with an ED50 value of 15.4 µg/mL. To compare the effect on the parasite with toxicity to mammalian cells, the cytotoxic activities of the isolated compounds against the KB cell line were evaluated and 10‐(chrysophanol‐7′‐yl)‐10‐(ξ )‐hydroxychrysopanol‐9‐anthrone and chryslandicin displayed very low toxicity with ED50 values of 104 and 90 µg/mL, respectively. This is the first report of the inhibition of the growth of P. falciparum by anthraquinone‐anthrone dimers and establishes them as a new class of potential antimalarial compounds with very little host cell toxicity.