Central
to spintronics is the interconversion between electronic
charge and spin currents, and this can arise from the chirality-induced
spin selectivity (CISS) effect. CISS is often studied as magnetoresistance
(MR) in two-terminal (2T) electronic nanodevices containing a chiral
(molecular) component and a ferromagnet. However, fundamental understanding
of when and how this MR can occur is lacking. Here, we uncover an
elementary mechanism that generates such an MR for nonlinear response.
It requires energy-dependent transport and energy relaxation within
the device. The sign of the MR depends on chirality, charge carrier
type, and bias direction. Additionally, we reveal how CISS can be
detected in the linear response regime in magnet-free 2T nanodevices,
either by forming a chirality-based spin-valve using two or more chiral
components or by Hanle spin precession in devices with a single chiral
component. Our results provide operation principles and design guidelines
for chirality-based spintronic nanodevices and technologies.