She was part of the Guerrillas of Theater groups in Spain setup by the Republican government. When Francisco Franco came to power she left her country as did many other artists and intellectuals. She arrived with her family in Mexico in 1939 and debuted in theater the following year in the play Mujeres. In 1940 she made her first film El capitán estrella and married Lucilo Gutiérrez next year. She retired from showbusiness for a decade and became a Mexican citizen in 1952.
She made approximately 38 telenovelas, 39 movies and 100 plays. Hugo Argüelles wrote La Ronda de la hechizada specifically for her in 1968. Ofelia Guilmain died at the age of 83 years old from respiratory failure caused by pneumonia.
