Blessy, who introduced her to film field, was the director of Calcutta News. Her next film was Calcutta News with Dileep. Media quoted her as, "Matching step with the megastar in this histrionic race is Meera Jasmine, who amazes you with a stunning delineation of her difficult role". Her performance as an innocent middle-class woman won praise from audiences.
The film was showcased in film festivals and won awards. She was next featured opposite Mammootty in the critically acclaimed film Ore Kadal. Her next film with Dileep – Vinodayathra, which again was directed by Sathyan Anthikkad. The film went on to become a commercial success. She played as a girl pretending to be a boy due to the pressure of circumstances in the first half of the film. She then paired with Mohanlal in Rasathanthram (2006). In the film Achuvinte Amma (2005), she enacted the young, adorable character Achu. It was followed by her performance as Raziya in Perumazhakkalam alongside Kavya Madhavan. She played a 15-year-old Muslim girl who was forced to marry an older man, for which she was awarded a State Award and the National Award in addition with several other awards. Chandran's acclaimed Padam Onnu Oru Vilapam. The film was a success at the box office, running for 100 days. She received her first Filmfare award for her performance in Kasthooriman. She rose to fame in Malayalam cinema with the film Kasthooriman directed by her mentor Lohithadas, in which she enacted comedy and sentimental scenes. Among the five main characters, the one who scored the most was again Meera. Her performance was appreciated and the film was a high commercial success. Her third film was Swapnakkoodu, a romantic comedy alongside Prithviraj, Kunchako Boban, Jayasurya, and Bhavana under director Kamal. Her role as a Jewish girl was appreciated by Malayalam critics. Her second film was Gramaphone, directed by Kamal, in which she appeared alongside Navya Nair and Dileep. Meera Jasmine made her debut in the Malayalam film Soothradharan. He initiated me into films with Soothradharan and I owe it all to him".
She also said that Lohithadas "is like a father figure and my guru. I never was the artistic type, I never thought I could dance, and I had not even thought of myself as being beautiful". Never in my wildest dreams did I imagine being in films. She stated, "I was just an ordinary girl. Meera had initially wanted to study and become a doctor and never had dreamed of becoming a film star. She had enrolled for a BSc degree in Zoology at Assumption College, Changanassery and completed nearly three months when she was spotted by director Blessy (who was then an assistant director to director Lohithadas) and offered a role in Soothradharan. She appeared for her Higher Secondary Exams in March 2000. She completed her schooling in Bala Vihar, Thiruvalla and Marthoma Residential School, Thiruvalla. She has two sisters, Jiby Sara Joseph and Jeny Susan Joseph, who has also acted in films, and two brothers, one of them, George worked as an assistant cinematographer. Meera Jasmine was born in Kuttapuzha village, Thiruvalla, Kerala to Joseph and Aleyamma.