His breakthrough as a leading actor came with the 1953 film "Manam Pola Mangalyam," where he played a dual role alongside actress Savitri, who later became his wife. This film marked the start of his rise to stardom, and from then on, he carved a niche for himself in Tamil cinema, focusing mainly on romantic characters over action roles.

Over a career spanning nearly five decades, Gemini Ganesan featured in over 200 films, portraying a wide range of roles from mythological figures like Krishna in "Mayabazar" (1957) to complex characters in socially significant films such as "Kappalottiya Thamizhan" (1961). He also made appearances in Hindi films, mostly remakes of his Tamil hits, including "Miss Mary" (1957).

His performance in his own production "Naan Avanillai" (1974), in which he played multiple roles as a seducer, garnered critical acclaim and a Filmfare Award for Best Tamil Actor.

Later in his career, he transitioned to television, notably appearing in the serial "Krishnadasi." Some of his final film appearances were in "Avvai Shanmugi" (1996), a Tamil remake of "Mrs. Doubtfire."

Gemini Ganesan is also credited with introducing the legendary Tamil actor Kamal Haasan to the film industry. He was recognized for his love and advocacy of the Tamil language, participating in cultural events like the World Tamil Conference.

His personal life included marrying Alamelu in 1940, with whom he had four daughters, and later marrying actress Savitri. He passed away on March 22, 2005, in Chennai, Tamil Nadu, at the age of 84 due to kidney failure and multiple organ dysfunction.