Abstract: To clarify the residues and decline dynamics of fluopimomide and dimethomorph in tobacco leaves, an efficient method using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established. Samples were extracted with acetonitrile and purified by dispersive solid-phase extraction. Then, they were separated by a Thermo Hypersil GOLD C18 column, eluted with acetonitrile-0.1% formic acid gradient, ionized by electrospray ionization source (ESI+), and monitored by multiple reaction monitoring (MRM). The results indicated that the method had a good linearity, with average recoveries of the two pesticides between 86% and 96% at levels of 0.02-20 mg/kg (fresh tobacco leaves) and 0.05-50 mg/kg (cured tobacco leaves), and relative standard deviations (RSDs) ranging from 3.0% to 9.4%. This method is simple, accurate, and highly feasible. Field experiments were conducted to study the decline dynamics of fluopimomide and dimethomorph in tobacco leaves, revealing that the decline dynamics of both pesticides followed the first-order kinetic model, with half-lives of 7.2-15 days and 5.3-12 days, respectively, indicating that both pesticides are readily degradable. The final residue levels 21 days after the last application were 0.050~6.246 mg/kg and 0.063~3.547 mg/kg, respectively. In this study, an HPLC-MS-MS detection method for fluopimomide and dimethomorph in tobacco leaves was established, elucidated their decline dynamics and final residues, which provided scientific evidence for their rational and safe use in tobacco cultivation and provided data support for the establishment of maximum residue limits of fluopimomide and dimethomorph in tobacco.