In athletics sprint events, the block start performance can be fundamental to the outcome of a race. This Systematic Review aims to identify biomechanical factors of critical importance to the block start and subsequent first two steps performance. A systematic search of relevant English-language articles was performed on three scientific databases (PubMed, SPORTDiscus, and Web of Science) to identify peer-reviewed articles published until June 2021. The keywords “Block Start”, “Track and Field”, “Sprint Running”, and “Kinetics and Kinematics” were paired with all possible combinations. Studies reporting biomechanical analysis of the block start and/or first two steps, with track and field sprinters and reporting PB100m were sought for inclusion and analysis. Thirty-six full-text articles were reviewed. Several biomechanical determinants of sprinters have been identified. In the “Set” position, an anthropometry-driven block setting facilitating the hip extension and a rear leg contribution should be encouraged. At the push-off, a rapid extension of both hips and greater force production seems to be important. After block exiting, shorter flight times and greater propulsive forces are the main features of best sprinters. This systematic review emphasizes important findings and recommendations that may be relevant for researchers and coaches. Future research should focus on upper limbs behavior and on the analysis of the training drills used to improve starting performance.