Elimination of unknowns in systems of equations, starting with Gaussian elimination, is a problem of general interest. The problem of finding an a priori upper bound for the number of differentiations in elimination of unknowns in a system of differential-algebraic equations (DAEs) is an important challenge, going back to Ritt (1932). The first characterization of this via an asymptotic analysis is due to Grigoriev’s result (1989) on quantifier elimination in differential fields, but the challenge still remained. In this paper, we present a new bound, which is a major improvement over the previously known results. We also present a new lower bound, which shows asymptotic tightness of our upper bound in low dimensions, which are frequently occurring in applications. Finally, we discuss applications of our results to designing new algorithms for elimination of unknowns in systems of DAEs.