From engine controls’ perspective, understanding autoignition dynamics is a key to enabling new combustion modes for internal combustion engines, especially for renewable fuels. Conventional autoignition investigations of fuels commonly involve a rapid compression of oxidizer-fuel mixture to a desired set of temperature-pressure conditions in a rapid compression machine (RCM), and subsequent measurement of the ignition delay. However, even for relatively close thermal states at the compressed condition, different thermodynamic paths (pressure-temperature histories) may lead to significantly different chemical kinetic states and hence significantly different ignition delay measurements. Currently, there exists no systematic method to study this path dependence of auto-ignition. In this work we present, for the first time, a systematic framework for investigation of the effect of small perturbations in the thermo-kinetic states, caused by perturbing the thermodynamic path of compression, on the ignition delay of fuels from a dynamical systems perspective. First, we introduce a novel controlled trajectory rapid compression and expansion machine (CT-RCEM) which offers the ability to precisely control the piston trajectory during compression of the fuel-oxidizer mixture, allowing the thermodynamic path to be tailored as desired. We use the CT-RCEM to experimentally investigate the influence of compression trajectory perturbation on the ignition delay of a specific fuel — dimethyl-ether (DME). Next, using a reduced order model of the combustion dynamics in the CT-RCEM that we developed, we investigate the evolution of the perturbation in the thermo-kinetic states resulting from trajectory perturbation to explain the experimental observations. Finally, we show that the sensitivity of auto-ignition to the thermodynamic path perturbation essentially arises from changes in the chemical reaction rates due to different amounts of intermediate species buildup for different thermodynamic paths.