Explaining the existence of super massive black holes (SMBHs) with MBH ≳ 108 M⊙ at z ≳ 6 is a persistent challenge to modern astrophysics. Multiwavelength observations of z ≳ 6 quasi-stellar objects (QSOs) reveal that, on average, their accretion physics is similar to that of their counterparts at lower redshift. However, QSOs showing properties that deviate from the general behavior can provide useful insights into the physical processes responsible for the rapid growth of SMBHs in the early universe. We present X-ray (XMM-Newton, 100 ks) follow-up observations of a z ≈ 6 QSO, J1641+3755, which was found to be remarkably X-ray bright in a 2018 Chandra dataset. J1641+3755 is not detected in the 2021 XMM-Newton observation, implying that its X-ray flux decreased by a factor ≳7 on a notably short timescale (i.e., ≈115 rest-frame days), making it the z > 4 QSO with the largest variability amplitude. We also obtained rest-frame ultraviolet (UV) spectroscopic and photometric data with the Large Binocular Telescope (LBT). Surprisingly, comparing our LBT photometry with archival data, we found that J1641+3755 became consistently brighter in the rest-frame UV band from 2003 to 2016, while no strong variation occurred from 2016 to 2021. Its rest-frame UV spectrum is consistent with the average spectrum of high-redshift QSOs. Multiple narrow absorption features are present, and several of them can be associated with an intervening system at z = 5.67. Several physical causes can explain the variability properties of J1641+3755, including intrinsic variations of the accretion rate, a small-scale obscuration event, gravitational lensing due to an intervening object, and an unrelated X-ray transient in a foreground galaxy in 2018. Accounting for all of the z > 6 QSOs with multiple X-ray observations separated by more that ten rest-frame days, we found an enhancement of strongly (i.e., by a factor > 3) X-ray variable objects compared to QSOs at later cosmic times. This finding may be related to the physics of fast accretion in high-redshift QSOs.