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Serpentines are common minerals in several major tectonic faults in a variety of geodynamic settings and have variable frictional strength and complex deformation processes. Here we present friction experiments carried out on a suite of serpentine samples that include veins of antigorite, lizardite and fibrous serpentine (chrysotile and polygonal serpentine) together with massive samples of retrograde (lizardite and chrysotile rich) and prograde (antigorite‐rich) serpentinites. These samples were characterized from the hand specimen down to the nanoscale to precisely constrain their mineralogical composition and are interpreted to represent typical fault rocks and host rocks in serpentine‐bearing shear zones, respectively. Experiments were performed at effective normal stress from 5 to 120 MPa, at temperatures of 25 °C and 170 °C and water‐saturated, i.e. under the faulting conditions of the brittle upper lithosphere. Friction of antigorite samples, either massive or vein, is relatively high μ = 0.53. Retrograde, massive serpentinites, constituted primarily of lizardite and fibrous serpentines are frictionally weak, μ = 0.30. End‐members lizardite and fibrous serpentines are even weaker, 0.15 < μ < 0.19, and this weakness is unchanged at high temperature. We document deformation of lizardite and fibrous serpentines occurring predominantly via mode II cracking, crystal/fiber folding, and frictional sliding, which account for the observed mechanical weakness. When combined with frictional reactivation analysis, our data provide mechanical evidence for fault weakness inferred from earthquake dip distributions at oceanic outer rises and low‐angle normal faults beneath rifted continental margins and at slow/ultraslow spreading mid‐ocean ridges.