Asteroid exploration missions must deal with large uncertainties in a target body’s gravity and shape as well as ephemeris errors upon rendezvous. Navigation and guidance are typically performed using ground-based operations, which can be costly. This paper studies the possibility of removing the ground in the process through onboard navigation with optical measurements and accelerometer-based measurements. The paper first describes the dynamics and measurement models used to simulate a spacecraft’s interaction with the asteroid environment, followed by implementation details of navigation and guidance subsystems. The paper then presents a covariance analysis of this problem using simplified dynamics, focusing on the information content of the optical and measurements. Guided by this, an end-to-end autonomous exploration scheme with onboard navigation and event-driven orbit control is analyzed through simulation, introducing realistic errors between the truth and filter dynamics. The basic operations of this scheme are built around near-inertial hovering and include approach from the end of an interplanetary phase, reconnaissance at various viewing geometries, close gravity estimation, and orbit insertion. The feasibility of the proposed autonomous navigation and orbit control is evaluated using a Monte Carlo analysis and is shown to be robust.