We perform long-term ($\approx 15$ yr, observed-frame) X-ray variability analyses of the 68 brightest radio-quiet active galactic nuclei (AGNs) in the 6 Ms $Chandra$ Deep Field-South (CDF-S) survey; the majority are in the redshift range of $0.6-3.1$, providing access to penetrating rest-frame X-rays up to $\approx 10-30$ keV. Twenty-four of the 68 sources are optical spectral type I AGNs, and the rest (44) are type II AGNs. The time scales 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 ($L_{\rm{X}}$) and absorption ($N_{\rm{H}}$) variability via spectral fitting. Most (74%) sources show $L_{\rm{X}}$ 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 $\lesssim 0.3$ pc. $L_{\rm{X}}$ variability is also detected in a broad absorption line (BAL) quasar. The $N_{\rm{H}}$ variability amplitude for our sample appears to rise as time separation increases. About 16% of sources show $N_{\rm{H}}$ 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.
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