She was born Gisèle Marie-Louise Marguerite LaFlèche in Winnipeg, Manitoba, and studied violin and voice at the Royal Conservatory in Toronto, Ontario. She had her own Canadian Broadcasting Corporation radio program, Meet Gisele, before moving to the Los Angeles, California area in 1951.

MacKenzie possessed a crystalline, resonant singing voice. It has been said that she was the greatest female vocalist of her generation. She recorded record albums and 45 rpm singles on various record labels, most notably Capitol and RCA. Her biggest selling song was "Hard To Get" in 1955.

MacKenzie was also an accomplished violinist and performed many comedic musical duets with mentor Jack Benny. She sang frequently on early television shows such as The Jack Benny Program, and The Ed Sullivan Show. She appeared often at Las Vegas venues in her burgeoning career and in numerous concerts throughout her life.

In the United States, she appeared on radio on such stars' programs as Bob Crosby and Mario Lanza. She also hosted a radio show entitled Airtime. In 1952 and 1953 she toured with Jack Benny, who recommended her for Your Hit Parade. During her tenure on Your Hit Parade the song "Hard to Get" became one of the chart hits. MacKenzie appeared on the show for several years, finally leaving in 1957 to head her own short-lived variety program, The Gisele MacKenzie Show. She returned to television in 1963, appearing as a regular on The Sid Caesar Show.

In later years MacKenzie performed widely in musical theater in such shows as Mame, Gypsy, The Sound of Music, and Hello Dolly. She turned to acting in the 1990s, making guest appearances on episodic television.