large-area electronics as switching elements are an ideal option for electrode-array-based digital microfluidics. with support of highly scalable thin-film semiconductor technology, high-resolution digital droplets (diameter around 100 μm) containing single-cell samples can be manipulated freely on a two-dimensional plane with programmable addressing logic. in addition, single-cell generation and manipulation as foundations for single-cell research demand ease of operation, multifunctionality, and accurate tools. in this work, we reported an active-matrix digital microfluidic platform for single-cell generation and manipulation. the active device contained 26,368 electrodes that could be independently addressed to perform parallel and simultaneous droplet generation and achieved single-cell manipulation. we demonstrate a high-resolution digital droplet generation with a droplet volume limit of 500 pl and show the continuous and stable movement of droplet-contained cells for over 1 h. furthermore, the success rate of single droplet formation was higher than 98%, generating tens of single cells within 10 s. in addition, a pristine single-cell generation rate of 29% was achieved without further selection procedures, and the droplets containing single cells could then be tested for on-chip cell culturing. after 20 h of culturing, about 12.5% of the single cells showed cell proliferation.