In modern manufacturing setups, linear motion systems are extensively used for producing straight-line motion with positional control. Applications such as computer numerical control (CNC) machining, precision laser printing, moving multi-axis robots, etc., feature linear motion systems. These systems, however, are susceptible to degradation and develop faults over prolonged usage. Structural health degradation of different system components gives rise to increased mechanical and thermal loads along with increased vibrations. This degradation eventually restricts the ability of linear motion systems to deliver the required quality of performance in terms of positional accuracy, precision, and reliability. Determining the location of degradation is important for maintaining the system’s components in a healthy state of operation. Furthermore, identifying the type and location of the faults generated through the degradation of one or more components is also instrumental for conducting repairs/replacements before the systems fail to deliver the required performance. Hence there is a need to develop prognostics and health management (PHM) methodologies capable of location-specific condition monitoring and location-specific fault classification. Data signals collected from motion controllers and external sensors are used to train machine learning algorithms that consider healthy state signals as the baseline and quantify the deviation of new signals from this baseline in terms of health indicators (HI). In this thesis, a PHM methodology is proposed for developing system health indicators (HI) using self-organizing maps and principal component analysis. Data preprocessing steps of signal extraction, signal segmentation, feature extraction, feature selection, and data normalization are followed by training baseline models for health indicators. These HI are then evaluated over signal data with unknown health, to monitor the gradual degradation of the linear motion system. The resulting values of HI are plotted with respect to the time of operation for early identification of the onset of degradation. This methodology is then applied for location-specific health evaluation of a linear motion system when it travels over a preselected point of interest. Linear motion systems exhibit different modes of failure based on the combination of components generating the degradation locally. Data collected from different combinations of degraded components can be used to build a multi-class fault classifier. In this thesis work, a PHM methodology is proposed that trains and evaluates a multi-class classifier capable of cross-speed regime fault classification using the fine-tuning method of transfer learning. Traditional machine learning classifiers along with convolutional neural networks are used for the same regime and cross-regime classification tasks.Ball screw systems are considered case studies to extract data and validate the proposed PHM methodologies in this thesis. Ball screw systems are widely used in the manufacturing industry owing to their capability of generating highly accurate and precise motion even at high torque loads. The lead screw and the linear guideways for carriage can degrade at different points over the stroke length of a ball screw. Hence, PHM methodologies of location-specific health monitoring and fault classification have been applied and evaluated over the data signals generated during ball screw operation.