Between 2004 and 2008 Daniel Apai has worked as a postdoctoral researcher at the Steward Observatory's NASA Astrobiology Institute node on high-contrast adaptive optics direct imaging searches for extrasolar planets.

In 2011, he moved back to faculty of the University of Arizona's Steward Observatory and Lunar and Planetary Laboratory, where he is full professor since 2021.

In two papers published in 2018[4] and 2019,[5] Apai, with his then-doctoral student Benjamin V. Rackham, and Mark Giampapa, provided the first systematic studies of the "transit light source effect" that leads to "stellar contamination" of exoplanet transmission spectra.

The papers correctly predicted that stellar contamination will be the limiting factor in the studies of small exoplanets with the James Webb Space Telescope.

In 2016, Apai assembled a group of optical scientists, astrophysicists, and aerospace engineers to address a key technological challenge to scaling up astronomical space telescopes, with the goal of proposing a novel space telescope to NASA to survey a thousand extrasolar planets for atmospheric signatures of life (biosignatures).

The first such unit space telescope, with a notional 8.5m-diameter lens, was proposed as the Nautilus Probe to the Astronomy 2020 Decadal Survey.