Rodríguez is known by many fans as "El Inolvidable" (The Unforgettable One), a moniker based on his most popular song, a bolero written by Cuban composer Julio Gutiérrez.

In 1936, 13-year-old Rodríguez joined the group of Ladislao (El Maestro Ladí) Martínez, Conjunto de Industrias Nativas, as a singer.

In 1952, he was honored for having developed his own unique singing style (early in his career he had been heavily influenced, as had so many other singers, by the Cuban vocalist Miguelito Valdés) by the "Century Conservatory of Music of New York".

Although described by historians and musicians alike (including both Titos) as "a friendly rivalry", their purported feud became a sort of urban legend in the world of Latin dance music.

[10] For example, Rodríguez's version of "Avísale a mi contrario" has been often cited as an example of this "feud",[2] despite the fact that the song was written by Ignacio Piñeiro in 1906.

Notably, he invited jazz players Bob Brookmeyer, Al Cohn, Zoot Sims and Clark Terry to appear with him in performances at New York City's famed Birdland nightclub.

[2] Rodríguez returned to Puerto Rico in 1966 and built a Japanese-style house in Ocean Park, Santurce, where he lived with his family.

Among the guest stars that appeared on his show were Sammy Davis Jr., Tony Bennett, Shirley Bassey, Roberto Clemente and Orlando Cepeda.

Rodríguez's last public appearance was with Machito and his band on February 2, 1973, at Madison Square Garden in New York City.

[9] Tito Rodríguez's Japanese-style house in Puerto Rico is featured on tours of the San Juan metropolitan area.