Having been advised as a child to begin swimming to combat asthma, the Brisbane schoolgirl broke into the Australian team for the 1991 World Championships in Perth, winning a silver medal in the medley relay. The following year, Riley won a bronze medal in the 100m breaststroke at the 1992 Barcelona Olympics, as well as competing in the 200m event.
Riley continued to sweep all before her in 1995, but arrived for the Atlanta Olympics under the cloud of a doping controversy. She had failed a drug test, and was only exonerated after her coach Scott Volkers admitted to giving her a headache tablet which contained the banned substance. Under the pressure of the controversy, Riley performed well outside her personal best times, which would have been enough for gold. She collected a bronze in the 100m breaststroke. She also collected a silver medal in the 4x100m relay with Nicole Stevenson, Susie O'Neill and Sarah Ryan.
Riley never stood on the podium again as an individual at the world level, but maintained her position in the Australian squad. Many anticipated her to return to her peak at the 2000 Sydney Olympics, but a kidney infection disrupted her training and she was ousted from the team at the Selection Trials by 14-year old prodigy Leisel Jones. She left the pool in tears, and subsequently retired.
At one stage during the mid-1990s, Riley was the girlfriend of Norwegian Olympic champion speedskater Johann Olav Koss. This sparked media speculation that he would compete for Australia at the Winter Olympics.
The major arterial Samantha Riley Drive in Beaumont Hills is named after her.