This study describes the development and validation of a simple, accurate and sensitive ultra high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method for the simultaneous quantification of 10 mycotoxins and 29 pesticides in ginseng. The method featured a fast and straightforward one-step extraction procedure using acetonitrile/water/formic acid (99:33:1, v/v/v) without further cleanup. Rapid LC separation in 8min was successfully achieved on a Phenomenex Kinetex C18 column (2.1mm×100mm, 2.6μm) with a flow rate of 0.30mL/min using a mobile phase of water containing 0.1% formic acid and methanol. Simultaneous acquisition was performed in the positive and negative ion modes. For some analytes, enhanced responses were acquired in negative ion mode (e.g., Zearalenone, α-Zearalenol and β-Zearalenol); however, the majority of analytes were monitored in positive ion mode with multiple reaction monitoring (MRM). Two MS/MS transitions for each analyte were acquired to ensure reliable identification and accurate quantification. The method was validated in house through linearity, selectivity, precision, and recovery studies. Analytical data were satisfactory with typical recoveries of 70-120% and relative standard deviations (RSDs) below 20%. The limits of detection (LODs) ranged from 0.01 to 0.25ng/mL, which are below the maximum residue levels (MRLs) established by European legislation for mycotoxins or pesticides in foods and foodstuffs. Forty-three ginseng samples (ginseng (n=30), American ginseng (n=6), red ginseng (n=7)) collected from Chinese markets were analyzed and the most frequently detected pesticide was chlorpyrifos with an incidence of 97% and ranged from 37.63 to 158.60μg/kg. Ion ratios, retention times and experimental Q/q ratios were also compared with those of the corresponding reference standard in order to avoid false-positive results.