Kate O’Neill and her twin sister Laura competed together at Milton High School in Milton, MA where they grew up. By the time she had graduated from high school, Kate had won one individual state title in the mile and three team state titles (one in the 4 x 800 relay and two in cross country).

After high school, Kate and her sister competed for Yale University. During her collegiate career, Kate was a seven-time All-American, ten-time Ivy League Champion, and was named the 2003 NCAA Woman of the Year for Connecticut. Kate finished second at the NCAA Championships three times during her senior year in cross country, the indoor 5000 meters, and the outdoor 10,000 meter events. Her athletic achievements were matched by her academic pursuits; she was awarded Academic All-American honors three times and was a two-time Academic All-Ivy.

Kate graduated from college in 2003 with the goal of qualifying for the 2004 Olympic Track Trials. She surprised herself, her coaches, and her family by surpassing this goal, dropping over a minute from her previous best in the 10,000 meters. Her time of 31:34 met the Olympic A qualifying standard. She later cinched her spot on the Olympic roster by finishing third at the 2004 Olympic Trials and finished the year ranked third for American women at the distance.

Following two years of injuries in 2005 and 2006, she shifted her focus to the marathon. In 2007, she started the year by finishing runner-up at the USA Half-Marathon Championships with a time of 1:11.47. Later that year, Kate overcame 90 degree heat at the LaSalle Bank Chicago Marathon to finish third in her debut at the distance (2:36:15).

Kate started 2008 by showing that she was a strong contender to make the US Olympic Marathon team by winning her first national championship. However, a knee injury suffered one month prior to the Trials thwarted her efforts. The injury forced her to drop out of the race. She returned from the injury and finished the year on a strong note by running a new personal best of 2:34:04 at the Chicago Marathon.

In 2009, Kate won the Cardinal Invitational 10,000 meters and placed 7th in the USA 15 km Championships during her preparation for the Flora London Marathon, where she ran 2:34:48 and placed 13th overall.