The high-pressure structural and vibrational properties of Bi2S3 have been probed up to 65 GPa with a combination of experimental and theoretical methods. The ambient-pressure Pnma structure is found to persist up to 50 GPa; further compression leads to structural disorder. Closer inspection of our structural and Raman spectroscopic results reveals notable compressibility changes in specific structural parameters of the Pnma phase beyond 4-6 GPa. By taking the available literature into account, we speculate that a second-order isostructural transition is realized near that pressure, originating probably from a topological modification of the Bi2S3 electronic structure near that pressure. Finally, the Bi(3+) lone-electron pair (LEP) stereochemical activity decreases against pressure increase; an utter vanishing, however, is not expected until 1 Mbar. This persistence of the Bi(3+) LEP activity in Bi2S3 can explain the absence of any structural transitions toward higher crystalline symmetries in the investigated pressure range.