American skullcap (Scutellaria lateriflora L.), a medicinal plant species valued for its sedative properties associated with flavonoids, is generally harvested from the wild. Scientific information on how field cultivation practices affect dry matter yield is lacking in this species. A 2 × 2 × 3 split plot factorial experiment within a randomized complete block design was conducted on a Marvyn loamy sand (fine-loamy, kaolinitic, Thermic Typic Kanhapludults) in Central Alabama to explore effects of light, irrigation, and nutrient application on dry matter yield of American skullcap. Treatment factors were shade (40% shade vs. no shade), irrigation (applied at 30 kPa vs. no irrigation), and nutrients [no added nutrients vs. nutrients added as chemical fertilizer (100 kg nitrogen, 68 kg phosphorus, 42 kg potassium/ha) or chicken litter (100 kg nitrogen, 50 kg phosphorus, and 123 kg potassium/ha)]. Shade formed the main plot units, whereas irrigation × nutrient factorial combinations were subplots. Skullcap shoots in experimental plots were harvested four times during the course of the two-year experiment (2007, 2008). All growth variables measured, except percent dry matter, performed better under shade than in full sun. Dry matter yield was increased 45% by shade, 61% by irrigation, and 22% by addition of nutrients. A significant irrigation × nutrients interaction was observed at the first and second harvests. Highest yields were obtained with the irrigation + manure and irrigation + fertilizer treatments under shade and the lowest with fertilizer and the control treatments in full sun.