The ball-screw feed drive has varying high-order dynamic characteristics due to flexibilities of the slender screw spindle and joints between components, and an obvious feature of non-collocated control when a direct position measurement using a linear scale is employed. The dynamic characteristics and non-collocated situation have long been the source of difficulties in motion and vibration control, and deteriorate the achieved accuracy of the axis motion. In this study, a dynamic model using a frequency-based substructure approach is established, considering the flexibilities and their variation. The position-dependent variation of the dynamic characteristics is then fully investigated. A corresponding control strategy, which is composed of a modal characteristic modifier (MCM) and an intelligent adaptive tuning algorithm (ATA), is then developed. The MCM utilizes a combination of peak filters and notch filters, thereby shaping the plant dynamics into a virtual collocated system and avoiding control spillover. An ATA using an artificial neural network (ANN) as a smooth parameter interpolator updates the parameters of the filters in real time in order to cope with the feed drive’s dynamic variation. Numerical verification of the effectiveness and robustness of the proposed strategy is shown for a real feed drive.