Conformational changes of filamin A under stress have been postulated to play crucial roles in signaling pathways of cell responses. Direct observation of conformational changes under stress is beyond the resolution of current experimental techniques. On the other hand, computational studies are mainly limited to either traditional molecular dynamics simulations of short durations and high forces or simulations of simplified models. Here we perform all-atom discrete molecular dynamics (DMD) simulations to study thermally and force-induced unfolding of filamin A. The high conformational sampling efficiency of DMD allows us to observe force-induced unfolding of filamin A Ig domains under physiological forces. The computationally identified critical unfolding forces agree well with experimental measurements. Despite a large heterogeneity in the population of force-induced intermediate states, we find a common initial unfolding intermediate in all the Ig domains of filamin, where the N-terminal strand unfolds. We also study the thermal unfolding of several filamin Ig-like domains. We find that thermally induced unfolding features an early-stage intermediate state similar to the one observed in force-induced unfolding and characterized by the N-terminal strand being unfurled. We propose that the N-terminal strand may act as a conformational switch that unfolds under physiological forces leading to exposure of cryptic binding sites, removal of native binding sites, and modulating the quaternary structure of domains.