Piper was born in Grosse Pointe, Michigan in 1983, the daughter of Kenneth and Carol Ann Piper. Her father works for General Dynamics, a defense contractor, and her mother is an aerobics instructor. Piper has one older sister, Cortney, who is also a swimmer and swam for the University of Tennessee. Piper is a 2001 graduate of Grosse Pointe North High School in Grosse Pointe Woods, Michigan. Piper attended the University of Wisconsin–Madison and graduated in 2006, majoring in zoology. At the University of Wisconsin–Madison, she had a highly successful career on the women's swimming team and served as the team's captain. She twice won Big Ten Conference swimmer of the year honors and was an 18-time All-American. While still in school, and after she had exhausted her athletic eligibility, she served as a volunteer assistant coach with the UW men’s and women’s swimming teams. Piper married swim coach Shane Ryan on May 16, 2014.
At the 2004 U.S. Olympic Team Trials, Piper qualified for the 2004 Summer Olympics by finishing 5th in the 200-meter freestyle. She also placed 6th in the 400-meter freestyle.
At the 2004 Summer Olympics in Athens, Greece Piper won a gold medal in the 4×200-meter freestyle relay with Natalie Coughlin, Kaitlin Sandeno, and Dana Vollmer that set the world record in the event. On December 20, 2004 it was declared "Carly Piper Day" in Piper's hometown of Grosse Pointe Woods, Michigan for her accomplishments in Athens.