To analyze pesticide residues, GC coupled with quadrupole-Orbitrap MS (GC-Orbitrap-MS) has become a powerful tool because of its unique characteristics of accurate mass full-spectrum acquisition, high resolution, fast acquisition rates, and overcoming matrix interference. This paper presents an efficiency evaluation of GC-Orbitrap-MS for identification and quantitation in the 352 pesticide residues analysis of chrysanthemum flowers in full-scan mode. A streamlined pretreatment approach using one-step extraction and dilution was used, which provided high-throughput processing and excellent recovery. The samples were extracted using acetonitrile. The extracted solution was purified by a Sin-QuEChERS Nano column to suppress the matrix in chrysanthemum flowers and determined by GC-Orbitrap-MS. The calibration curves for the 352 pesticides obtained by GC-Orbitrap-MS were linear in the range of 0.5-200 g·kg, with the correlation coefficients higher than 0.99. The limits of detection (LODs) and the limits of quantification (LOQs) for the 352 pesticide residues were 0.3-3.0 g·kg and 1.0-10.0 g·kg, respectively. The average recoveries in chrysanthemum flower at three levels were 95.2%, 88.6%, and 95.7%, respectively, with relative standard deviations (RSDs) of 7.1%, 7.5%, and 7.2%, respectively. Lastly, the validated method and retrospective analysis was applied to a total of 200 chrysanthemum flower samples bought in local pharmacies. The proposed method can simultaneously detect multipesticide residues with a good performance in qualitative and quantitative detection.