Cognitive decline is common in the elderly. As a result, a range of cognitive rehabilitation games have been proposed to supplement or replace traditional rehabilitative training by offering benefits such as improved engagement. In this paper, we focus on mild cognitive impairment (MCI), an initial stage of cognitive decline that does not affect functioning in daily life, but which may progress towards more serious cognitive deteriorations, notably dementia. Unfortunately, while a variety of serious game frameworks and rehabilitative serious games have been proposed, there is a distinct lack of those which support the distinctive characteristics of MCI patients. Consequently, to optimise the advantages of serious games for MCI, we propose the MCI-GaTE (MCI-Game Therapy Experience) framework that may be used to develop serious games as effective cognitive and physical rehabilitation tools. The framework is derived from a combination of a survey of related research literature in the area, analysis of resident profiles from a nursing home, and in-depth interviews with occupational therapists (OTs) who work with MCI patients on a daily basis. The conceptual framework comprises four sectors that may be used to guide game design and development: an MCI player profile that represents the capabilities of a player with MCI, core gaming elements that support gameful and playful activities, therapeutic elements that support cognitive and physical rehabilitation through tasks and scenarios according to the player’s abilities, and motivational elements to enhance the player’s attitude towards the serious tasks. Together, they provide support for rehabilitation needs and may also serve as a set of comprehensive and established criteria by which an MCI serious game may be evaluated. To demonstrate the use of MCI-GaTE, we also present A-go!, an immersive gesture-based serious game that exploits the framework to enable MCI-diagnosed players to undertake therapeutic tasks supported by an assigned OT. Evaluation with OTs revealed that the immersive game potentially offers more effective support to MCI patients than traditional methods, contributing new possibilities for enhancing MCI rehabilitative training, while a comparative assessment of MCI-GaTE demonstrated that it provides a comprehensive approach not currently offered by state-of-the-art rehabilitative frameworks.