Liquid chromatography coupled to mass spectrometry (LC-MS), tandem mass spectrometry (LC-MS/MS), and high resolution mass spectrometry (LC-HRMS) today are among the most common techniques to guarantee food integrity and authenticity. Targeted approaches, where a family of characteristic bioactive substances in the analyzed food products are monitored, are a common practice to ensure food authenticity regarding the production region since bioactive substances content and distribution in food depend on multiple parameters such as climate conditions, water resources, agrochemical practices, etc. On the other hand, non-targeted approaches, such as metabolomic fingerprinting, are a common practice where a huge number of spectral detected variables in the analyzed foods are monitored. In both approaches, characteristic patterns are searched among the analyzed food products by means of statistical chemometric methods to address food characterization, classification, and authentication. In the present chapter, the role of LC-MS in combination with chemometrics to guarantee food integrity and authenticity will be discussed. Coverage of all kinds of applications is beyond the scope of the present contribution, so we will focus on the most relevant applications published in the last years by addressing the most interesting examples and important aspects in the food authenticity field.