Recent experiments on FeSe films grown on SrTiO3 (STO) suggest that interface effects can be used as a means to reach superconducting critical temperatures (T-c) of up to 80 K (ref. 1). This is nearly ten times the T-c of bulk FeSe and higher than the record value of 56 K for known bulk Fe-based superconductors(2). Together with recent studies of superconductivity at oxide heterostructure interfaces(3-6), these results rekindle the long-standing idea that electron pairing at interfaces between two different materials can be tailored to achieve high-temperature superconductivity(7-12). Subsequent angle-resolved photoemission spectroscopy measurements of the FeSe = STO system revealed an electronic structure distinct from bulk FeSe (refs 13,14), with an energy gap vanishing at around 65 K. However, ex situ electrical transport measurements(1,15) have so far detected zero resistance-the key experimental signature of superconductivity-only below 30 K. Here, we report the observation of superconductivity with T-c above 100 K in the FeSe = STO system by means of in situ four-point probe electrical transport measurements. This finding confirms FeSe/STO as an ideal material for studying high-T-c superconductivity.