The piezoelectricity of functionalized MXenes is of increasingly interest in theoretical and experimental research due to many advantages, such as narrowing the electromechanical coupling size, enhancing the piezoelectric coefficients and producing the out-of-plane piezoelectricity. In this work, employing the first-principle calculations, the piezoelectricity together with related electronic and elastic properties of six functionalized MXenes Sc2CTT′ monolayers where T and T′ are functional groups were comprehensively investigated. All of them are mechanically stable and more flexible than graphene, indicating their potential use in flexible devices. Furthermore, the semiconducting nature and broken inversion symmetry endow them with piezoelectricity for nanoelectromechanical facilities. In terms of the in-plane piezoelectricity, Sc2CFCl possesses the biggest d22 and Sc2COHH has the biggest d15. Sc2CHCl and Sc2CFCl monolayers have stronger out-of-plane piezoelectricity when the strain is applied along the x axis due to their larger absolute value of d31 than other monolayers. In addition, with relative to MoSTe which has relatively good out-of-plane piezoelectricity, Sc2COHF and Sc2CHCl monolayers possess comparable out-of-plane piezoelectric strain coefficient d33, which is favorable for their applications in out-of-plane piezoelectric sensing. Excitingly, the value of d33 (35.64 pm/V) for Sc2COHH monolayer is surprisingly over three times of that for MoSTe. It is expected that the studied Sc2CTT’ monolayers with commendable piezoelectric properties can be utilized in certain nanoelectromechanical systems, such as the blood-pressure meter, bionic skin of robots and energy harvesting equipments.