Long-term monitoring of PSR J2021+4026 in the heart of the Cygnus region with the Fermi Large Area Telescope unveiled a sudden decrease in flux above 100 MeV over a timescale shorter than a week. The "jump" was near MJD 55850 (2011 October 16), with the flux decreasing from (8.33 ± 0.08) × 10–10 erg cm–2 s–1 to (6.86 ± 0.13) × 10–10 erg cm–2 s–1. Simultaneously, the frequency spindown rate increased from (7.8 ± 0.1) × 10–13 Hz s–1 to (8.1 ± 0.1) × 10–13 Hz s–1. Significant (>5σ) changes in the pulse profile and marginal (<3σ) changes in the emission spectrum occurred at the same time. There is also evidence for a small, steady flux increase over the 3 yr preceding MJD 55850. This is the first observation at γ-ray energies of mode changes and intermittent behavior, observed at radio wavelengths for other pulsars. We argue that the change in pulsed γ-ray emission is due to a change in emission beaming and we speculate that it is precipitated by a shift in the magnetic field structure, leading to a change of either effective magnetic inclination or effective current.