At the age of 14, Seebohm won the 100 m backstroke at the 2007 Australian Championships, the selection meet for the 2007 World Aquatics Championships. At the World Championships in Melbourne, Seebohm won a gold medal in the 4 × 100 m medley relay. She also placed fourth in the final of the 100 m backstroke and 14th in the 50 m backstroke. Seebohm also won gold in both the 100 m backstroke and 4 × 100 m medley relay at the 2007 Junior Pan Pacific Swimming Championships. On 6 March 2008 at the Brisbane Catholic Schoolgirls Championships, Seebohm broke the 50 m backstroke Commonwealth and Australian records with a time 28.10 seconds, missing Li Yang's then world record of 28.09 by one hundredth of a second. On 22 March 2008, Seebohm broke the world record in the 50 m backstroke in the semi-finals of the 2008 Australian Championships, with a time of 27.95s, taking five hundredths of a second off Hayley McGregory's world record of 28.00 set only 15 days earlier on 7 March 2008. A day later, this record was beaten again, this time by Australian Sophie Edington in a time of 27.67 seconds in the final of the same event. Seebohm decided not to swim in the final of this event as it is not an Olympic event and instead decided to focus on the semi-final of the 100 m backstroke. Her decision paid off when she became the first Australian woman to break the one-minute barrier in the event, her 59.78 making her the fifth-fastest of all-time. She then lowered the record to 59.58 s in the final, winning the Australian championship and gaining selection for the Olympic Games in Beijing. At the 2008 Summer Olympics, Seebohm placed ninth overall in the 100 m backstroke, barely missing a spot in the final. Seebohm then swam in both the preliminaries and final of the 4 × 100 m medley relay, in which Australia won the gold medal. At the 2009 World Aquatics Championships in Rome, Seebohm won the bronze medal in the 100 m backstroke with a time of 58.88. She also won silver in the 4 × 100 m medley relay, and placed 7th in the 50 m backstroke and 15th in the 200 m IM. At the 2009 Australian Short Course Championships, Seebohm broke the world record in the 100 m IM in 58.54. At the 2010 Pan Pacific Swimming Championships, on the first night she defeated Olympic champion Natalie Coughlin in the 100 m backstroke, taking gold in championship record time, as well as taking silver in the 50 m butterfly. On the second night, she took silver in the 100 m freestyle in her first attempt at the event at international level. On night 3 she took another silver in the 4 × 100 m freestyle relay. Final night saw her take the gold in the 200 m individual medley, topping world champion and record holder Ariana Kukors. Later on in the night she broke the 100 m backstroke championship record in the lead off leg of the 4 × 100 m medley relay, Australia finished with silver. Later on in the year she collected 8 medals at the 2010 Commonwealth Games Seebohm was tracked by the BBC as part of their series World Olympic Dreams, which followed her as she prepared for London 2012. At the 2012 London Olympics, Seebohm set a new Olympic record in a 100m backstroke qualifier and was heavily backed to win the gold in the final of the event but fell just short and gained a silver medal. At the 2013 Australian Swimming Championships she won gold in the 50 m and 100 m backstroke and silver in 200 m individual medley and bronze in the 200 m backstroke events, qualifying for the 2013 World Aquatics Championships. At the World Championships, she teamed up with Bronte Campbell, Emma McKeon and Brittany Elmslie in the heats of the 4 × 100 m freestyle, finishing second in their heat and overall. In the final sisters Cate and Bronte Campbell, Emma McKeon and Alicia Coutts won the silver medal, finishing 0.12 seconds behind the United States. At the 2016 Summer Olympics, Seebohm represented Australia in both the 100 m and 200 m backstroke and won silver in the 4×100m medley relay.
