This study was conducted to investigate the residual loss of chlorpyrifos and the amount transferred to lettuce from soil. Field trials on lettuce were conducted in two different greenhouses located in Yongin (field 1) and Gwangju (field 2) in Korea. Soil and lettuce samples were collected on different days after the treatment of chlorpyrifos at two different levels. The initial residue of chlorpyrifos (0.86 and 2.31 mg/kg) in soils decreased to 0.06 and 0.18 mg/kg, respectively, at 36 days after treatment (DAT) in field 1, and the initial residue with values of 11.10 and 22.59 mg/kg decreased to 1.20 and 3.04 mg/kg, respectively, at 43 DAT in field 2. In field 1, the half-lives of chlorpyrifos were approximately 8.4 and 9.0 days for soils treated with 0.86 and 2.31 mg/kg, respectively, while in field 2, the half-lives of chlorpyrifos were approximately 18.7 and 13.9 days for soils treated with 11.10 and 22.59 mg/kg, respectively. Residue levels of chlorpyrifos on lettuce were 0.66–5.98% and 2.71–13.26% compared to the initial concentration in the soil. Therefore, the management guideline of chlorpyrifos for lettuce-cultivating soils could be suggested to be 0.75 mg/kg with regards to the Positive List System level of chlorpyrifos on lettuce of 0.01 mg/kg.