De Bruijn debuted at the World Aquatics Championships in January 1991, winning a bronze medal with the 4×100 m relay team, with which she won the gold medal at the European LC Championships in August of that year.
The following year, de Bruijn made her Olympic debut at the 1992 Summer Olympics, and finished 8th in the 100 m and 4×100 m freestyle events. She did not compete at the 1996 Summer Olympics. In 1999, she won the 50 m freestyle at the European Championships. The following year, after having swum several 50 m freestyle world records, she competed in the 2000 Summer Olympics in Sydney, Australia. She won the 50 and 100 m freestyle, and the 100 m butterfly, setting world records in all three events. She also won a silver medal with the 4×100 m freestyle relay team. Her nickname became "Invincible Inky".
She was named by Swimming World as the "Female World Swimmer of the Year" in both 2000 and 2001. She won titles in three events at the 2001 World Championships. At the 2003 World Championships, de Bruijn successfully defended her 50 m freestyle and butterfly titles. At the 2004 Summer Olympics in Athens she defended her gold medal in the 50 m free, and took silver in the 100 m free, and two bronze: one in the 100 m butterfly and another in the 4×100 m relay.
With an Olympic medal total of four gold, two silver and two bronze, she is the second most successful Dutch Olympian of all time. Moreover, her combined nine individual titles won at theOlympics (four) and World Aquatics Championships (five) are a record for female swimmers.
In March 2007, de Bruijn announced her retirement from competitive swimming.
She was the face for Dutch lingerie brand Sapph, along with kickboxer Remy Bonjasky, the face for the men's line of the brand.