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The subject of this study is strike-slip fault zones, where temporal variations of accumulation in strike-slip deformation complicate the standard process of deformation accumulation and release during strong earthquakes. These temporal variations are expressed in the El Ghab segment of the Dead Sea Transform zone (DST, Eastern Mediterranean) and in the Talas-Fergana fault zone (Central Asia). According to Global Positioning System (GPS) data, the strike-slip deformations within these zones are not now accumulating or are accumulating at a rate that is significantly less than their average rate during the Holocene and Quaternary or the Pliocene–Quaternary. Simultaneously, weak transverse shortening has been measured in both zones by GPS. In both of these zones, strong earthquakes have not registered within the XX century, yet epochs of intensified seismicity (strong earthquakes) took place throughout history. In the southern and central parts of the El Ghab zone, there is evidence of 30 strong historical earthquakes of Ms ≥ 5.7; however, no instrumental earthquakes of Ms ≥ 5 have been identified. The temporal distribution of seismic energy released by these earthquakes demonstrates a 350 ± 50-year cycle. Values for the seismic energies released during the peak phases of these cycles are approximated by a sinusoid that suggests the possibility of a ≥1800-year cycle (“hyper-cycle”), which began around the 3rd century, reached its maximum in the 12th century, and has continued until now. A combination of geological, archaeoseismological, and geodetic data show that the rate of sinistral strike-slip deformation varied in the fault zone, probably in conformity with the variation of seismicity during the “hyper-cycle.” In the Talas-Fergana fault zone, trenching and 14C dating that was correlated with right lateral offsets, gave a possible preliminary estimate of the average rates of the Late Holocene strike slip of about 10 mm per year, with a decrease in the SE direction to 4 mm–4.5 mm per year. These studies also showed that the slip in the Talas-Fergana fault zone was realized mainly during strong earthquakes. New trenching and 14C dating of paleoearthquake records identified the epoch of seismicity intensification dating to the XIV–XVII centuries. These paleoearthquakes could produce a total dextral slip at several meters. Therefore, consideration of these epochs was necessary to determine a calculated average slip rate during the Late Holocene. The main shock and the strongest aftershocks of the Altai earthquake of September 27, 2003, with Ms = 7.0 demonstrated a strike-slip focal mechanism with an NW-trending plane of the right lateral slip. An approximately 65 km-long NW-trending seismic rupture with a right lateral slip of up to 2 m, formed during the earthquake. The aftershock activity significantly decreased in 2004–2005 when reverse and rarer normal focal mechanisms became dominant. In the Palmyrides and the southern Aleppo block (NW Syria), strong earthquakes in 1994 (Mw = 5.3) and 1996 (Mw = 5.5) had strike-slip focal mechanisms, while only weak (magnitudes 1.1 to 3.3) earthquakes occurred in 2009–2011; the overwhelming majority of these weak earthquakes had normal and reverse mechanisms. In all of the cases mentioned above, strike-slip deformation was expressed only or mainly during strong earthquakes. At other times, the rate of its accumulation was small and the dominant stress conditions led to transverse shortening, rarely resulting in local lengthening of the tectonic zone. These variations are caused by the tectonic peculiarities of these zones. The sinistral component of the deformation is related to the shift of the Arabian Plate relative to the African one, but also the transverse component is related to the continental slope and is expressed by the Coastal range shortening that exists in the El Ghab segment zone. There is not only a dextral deformation component, but also a transverse component, expressed by shortening of the Fergana and Talas ranges existing in the Talas-Fergana fault zone. In both zones, the shortening component became appreciable or dominant when the strike-slip deformation rate decreased. Similar, but more local, relationships were expressed in the epicentral area of the 2003 Altai earthquake and in the Western Palmyrides.