We perform long-term (approximate to 15 years, observed-frame) X-ray variability analyses of the 68 brightest radio-quiet active galactic nuclei (AGNs) in the 6 Ms Chandra Deep Field-South survey; the majority are in the redshift range of 0.6-3.1, providing access to penetrating rest-frame X-rays up to approximate to 10-30 keV. Of the 68 sources, 24 are optical spectral type. I AGNs, and the rest (44) are type II AGNs. The timescales probed in this work are among the longest for X-ray variability studies of distant AGNs. Photometric analyses reveal widespread photon flux variability: 90% of AGNs are variable above a 95% confidence level, including many X-ray obscured AGNs and several optically classified type II quasars. We characterize the intrinsic X-ray luminosity (L-X) and absorption (N-H) variability via spectral fitting. Most (74%) sources show LX variability; the variability amplitudes are generally smaller for quasars. A Compton-thick candidate AGN shows variability of its high-energy X-ray flux, indicating the size of reflecting material to be less than or similar to 0.3 pc. L-X variability is also detected in a broad absorption line quasar. The NH variability amplitude for our sample appears to rise as time separation increases. About 16% of sources show NH variability. One source transitions from an X-ray unobscured to obscured state, while its optical classification remains type I; this behavior indicates the X-ray eclipsing material is not large enough to obscure the whole broad-line region.