Purtscheller pioneered climbing without a mountain guide, who in the 19th century did all the route finding and lead climbing. By the end of his life he had recorded climbing over 1,700 mountains. A celebrated climb was the traverse of the Meije together with the Zsigmondy brothers in 1885, which to this date is considered a classic alpine route. He is best known for his first ascent of Kilimanjaro in 1889, together with the German mountaineer Hans Meyer.
After a descent of the Aiguille du Dru with G. Löwenbach and Jakob Oberhollenzer on August 25, 1899, an ice axe broke and the rope team fell into a bergschrund. Purtscheller was injured and he was transferred to a hospital in Geneva and later Bern. After several months of recovery, he contracted pneumonia and died on the approximate date of his planned return home. In a eulogy, the American climber and mountain historian W.A.B. Coolidge called him "the greatest mountaineer who had ever lived".