Tsu was born in Shanghai, China to Z.M. and Dulcie Lynn Tsu. Her father was a banker and her mother a Painter. After political changes in China in the 1940s, the family left for Taiwan, then Hong Kong. Her father remained behind in Taiwan while in 1957 she and the rest of her immediate family (sister and mother) emigrated to Larchmont, New York, a suburb of New York City, where her aunt lived. Irene attended Mamaroneck Elementary School in Mamaroneck, New York and studied ballet.

In the late 1950s. she auditioned for a dancing job in Broadway's Flower Drum Song. A staff member of the Producer David Merrick's office saw the performance and auditioned her for the Broadway musical "The World of Suzie Wong" and Tsu got a part. Later Irene auditioned for Choreographer Hermes Pan in the upcoming film adaptation of the musical Flower Drum Song. The Choreographer Hermes Pan brought Irene to Hollywood and she was a teenage Dancer in the film Flower Drum Song (1961), directed by Henry Koster. He gave her her first speaking role as a teenage prostitute in his next film, Take Her, She's Mine (1963) starring James Stewart and Sandra Dee, which started her acting career.

In the 1960s, Tsu met Frank Sinatra in Miami, Florida where she was filming the "Chevron Island" commercials and Sinatra was filming "Tony Rome". They dated for over two years.

In 1961, Tsu entered the Miss Chinatown USA beauty pageant on behalf of New York and won first place.

On November 21, 1963, the evening before President John F. Kennedy was assassinated, Tsu's only appearance on Perry Mason was aired on CBS, as she played the role of defendant Juli Eng in "The Case of the Floating Stones." She made guest appearances on most of the other popular '60s-70s television shows such as I Spy, The Man From U.N.C.L.E., Voyage to the Bottom of the Sea, Family Affair, Mission: Impossible, and The Wild Wild West. She was tested for, but didn't get the female lead of The Sand Pebbles.

From 1978 until 1989, Tsu was Chief Operating Officer and head designer for her own leisure apparel company, The IT Company/Irene Tsu Designs.

Since 1990 Irene has been a realtor for Coldwell Banker in Beverly Hills, California. She is a single mother to her daughter, Yasmine, and a yoga practitioner for more than 25 years. Irene studied for many years directly with yoga master Bikram Choudhury and is featured in both of his books Bikram's Beginning Yoga Class. She taught at Bikram Yoga College in Encinitas, California. She teaches weekly yoga classes at the Bikram HQ in Los Angeles and for the Beverly Hills Department of Parks.