Pantani was born in Cesena, Romagna.

At 1.72 m and just 57 kg (5 ft 8 in, 126 lb/9 st), Pantani was a classically built mountain climber. In 1994, during his second participation to the Giro d'Italia, he became known after winning two mountain stages and finishing 2nd overall after Eugeni Berzin and before Miguel Indurain, who had won the last two editions of the Giro. He would probably have won that Giro if his team had not asked him to help their leader, Claudio Chiappucci, during the first mountain stages, where he lost a lot of time to Berzin. Pantani made his Tour de France debut in 1994 finishing 3rd overall, but he did not win a single stage even though he attacked - and left behind, Indurain (the Tour's eventual winner), during several stages. In 1995 he could not participate in the Giro because of an accident, the first of a long series, but he was back in the Tour and he won two stages, at Guzet Neige and at Alpe d'Huez. He also finished third in 1995's World Cycling Championship.

During the early years of Pantani's career he created a sensation with his unique style of climbing. Even though he often lost a lot of time during individual time trials, no one could compete with him in the high mountains. He impressed the other cyclists so much that, during a stage in Tour de France one of them clapped his hands as he was overtaken by Pantani. His determination to win, which made him take big risks downhill and often arrive at the top of a mountain pass close to anoxia, can be explained by the way he answered a journalist who asked why he was so fast during a climb: "to make my suffering end sooner."

Pantani's climbing style consisted of staying on the drops the entire way, often while pedaling out of the saddle. He preferred this position so much that Bianchi built him a special bike with a very high head-tube to accommodate a higher handlebar position. Just when he looked set to build on this success, Pantani was in a horrific collision during the Italian Milano-Torino race near the end of the 1995 season. He broke his leg in two places and faced the prospect of ending his career.