Thyagaraja, a saint and a poet, overcomes many hurdles in his life, including grinding poverty to emerge as the greatest Carnatic music composers of all time.

Murthy and Kalyani are happily married till Murthy watches a street play in his village and notices the beautiful Subbalaxmi in that troupe. He advises Subbalaxmi's father to take her to Madras, where she could possibly become a big theatre artiste. After traveling to Madras, Subbalaxmi is offered the lead role and changes her name to Sujatha. Murthy falls for Sujatha's charms and neglects his family.

Two siblings turn inseparable after the death of their parents. Things take a turn after they get married to their respective partners.

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The story revolves around the dangers of superstition, particularly when it concerns marriage and how unscrupulous elements in society could manipulate these beliefs to their benefit and lead to tragic consequences.

Immadi Pulikeshi is based on the story of the famous Kannada ruler Pulakeshin II of the Chalukya dynasty, who was significantly involved in branching out the dynasty to extend over most parts of the Deccan.