In situ TEM promises to supplement conventional static (S)TEM imaging to provide direct observation of dynamic processes at the nanometer or atomic scale. This technique has been bolstered by the introduction of fast CMOS-based detectors, which can acquire “movies” much faster than older CCD-based cameras. However, observation of very high-speed processes remains challenging due to insufficient camera framerate, deleterious rolling shutter artifacts, and inadequate signal-to-noise ratio (SNR) at the low electron exposure in each high-speed movie frame. To address these challenges, we have introduced a large-format direct detection TEM camera, capable of running at up to several thousand frames-per-second with ultra-low noise and the choice of either a rolling or global shutter, for higher speed or reduction of image artifacts, respectively. This camera enables robust in situ TEM observation of very fast specimen dynamics.