Ek Nayi Choti Si Zindagi is the tale of two sisters Isha and Ira. Separated by cicrcumstances, destiny brings the siblings together later in life.
Isha works at a radio station as RJ Palak. Her only aim in joining the radio station is to find her sister, Ira. She hopes and prays Ira will listen to her and recognize her.
Ira grows up to be a rich and spoil brat. However, there is a humane side to her too. She grows up hating Isha as she believes her sister chose Sam over her.
Angry with her past, Ira erases all memories of her childhood and even assumes a new identity. However, destiny brings Isha and Ira together once again. Unaware of their shared past, the duo meet and become best friends.
Fate brings Samarth Ojha and Isha together too when he joins Isha's radio station as a trainee. Isha was an inmate at the orphanage run by Samarth's grandmother Chetana until it was destroyed in a fire.
Isha makes another discovery: Sam and Ira are best friends and their mothers are planning their marriage. The arrival of Isha pours water over Revati's plans as she fears Isha has come back to destroy Ira's life.
Destiny brings Sam and Isha close. However, Ira's love for Sam places Isha in a quandary. Will she sacrifice her love for her sister?