In high school, Kastor won three California state cross country titles and two CIF California State Meet titles at 3200 meters while running for Agoura High School in Agoura Hills, California.  She also competed in the Foot Locker Cross Country Championships all four years of her prep career, and competed in both the North American Youth Maccabi Games and the Pan-American Maccabiah while in high school.

At the University of Arkansas she was a four-time SEC champion and an eight-time All-American. Post-collegiately, Kastor ran under coaches Joe Vigil and Terrence Mahon (currently head of the Mammoth Lakes, California training group).

Kastor has earned two silver medals (2002 Dublin, long race; 2003 Lausanne, long race) in the IAAF World Cross Country Championships.

She holds U.S. records in the following events:

Women's marathon (set when winning the 2006 Flora London Marathon with a time of 2:19:36)

Women's road 10 mile (set at the 2006 Berlin Half Marathon with a time of 51:31)[8]

Women's road 15K (set at the 2003 Gate River Run in Jacksonville with a time of 47:15)

Women's road 8K (set at the 2005 The LaSalle Bank Shamrock Shuffle in Chicago with a time of 24:36)

Kastor formerly held the following records:

Women's half marathon (set at the 2006 Berlin Half Marathon with a time of 1:07:34)

Women's 10,000 metres (set at Stanford in 2002 with a time of 30:50.32)

Women's road 5K (set at the 2002 Carlsbad 5000 with a time of 14:54)

In recent years, Kastor has shifted her focus toward the marathon distance. After winning the bronze medal at the 2004 Olympic Marathon, she won the 2005 Chicago Marathon. In 2006, she won the London Marathon, setting an American record. She placed sixth at the 2006 New York City Marathon and fifth at the 2007 Boston Marathon. Kastor is a featured subject in the 2007 marathon documentary Spirit of the Marathon, which follows her victory at the 2005 Chicago Marathon.