Melicope knudsenii is a medium-sized tree growing 3–10(–13) meters tall. Trunks may reach up to 30 cm in diameter, with smooth gray bark. New growth is densely tomentose with yellowish brown to olive brown hairs. Branches are also tomentose, becoming less hairy over time. The leaves are simple and opposite, with oblong–ovate to oblong–elliptic or elliptic blades measuring 9–25 cm long and 4.5–10 cm wide. The apex is obtuse to rounded, sometimes with a small notch (emarginate), and the base is weakly cordate, with basal lobes that may appear fused. The upper leaf surface is mostly glabrous except for sparse hairs on the midrib, while the lower surface is densely covered in olive brown tomentose hairs. Margins are entire. Venation is pinnate, with 12–16 pairs of lateral veins that curve and are connected by an arched submarginal vein 2–16 mm from the margin; higher-order veins form a reticulate pattern. Petioles are 20–60 mm long. Stipules are absent. The flowers are arranged in dense axillary cymes with 20–200 flowers per cluster, measuring 3–15 cm long. The entire inflorescence is densely tomentose. Bracteoles are deltate to lanceolate, and peduncles are stiff, angular, and 30–60 mm long. Pedicels are 3–5 mm long. Flowers may be bisexual (perfect) or potentially unisexual. Sepals are deltate, 3–4 mm long, densely silky gray, and persistent in fruit. Petals are oblong–ovate, 5–6 mm long, with a similar silky texture. There are 8 stamens in two whorls; they remain present but reduced in functionally female flowers. The ovary is superior and either glabrous or pilose on the lower half, with a single style (~4 mm) and four short stigmatic branches (~2 mm). The ovary is 4-celled and 4-lobed, with two ovules per cell. The fruits are composed of distinct follicles, 8–14 mm long, forming a fruit 18–30 mm wide. The exocarp is glabrous and glandular-punctate; the endocarp is also glabrous. Carpels dehisce along the upper suture. Seeds number 1–2 per follicle, measuring 5–6 mm long, glossy black when mature, ovoid, and may be angled due to compression. The seed coat is crustaceous, with a straight embryo embedded in fleshy endosperm. The cotyledons are ovate and compressed, and the radicle is short. It occurs in dry to mesic forest habitats between 910-1,000 meters.