Aamir Khan as Ranchhoddas "Rancho" Shamaldas Chanchad / Chhote / Phunsukh Wangdu, one of the titular trio in the engineering college who vanishes after graduation and whom his two friends hunt for ten years while telling stories of their time in college together. Rancho was a prodigal student with contempt for the inhumanity of the college's system. At the end of the film, he is shown to be a famous scientist, entrepreneur and businessman with 400 patents who also teaches young children when he takes a break from researching.
R. Madhavan as Farhan Qureshi, the film's narrator and one of the trio whose father persuades him to study engineering over his dream career of wildlife photography; in the end, he is shown to have published several books of photographs.
Sharman Joshi as Raju Rastogi, another of the trio who comes from an impoverished family with a mother who is a retired school teacher and a paralysed father who worked as a postmaster. Previously, his family was unable to afford the car that would be demanded as a dowry for his sister; in the present, however, he is a settled married man in Delhi who has freed his family from poverty by becoming a wealthy business executive and engineer.
Boman Irani as Dr. Viru "Virus" Sahastrabuddhe, the college's strict director and Pia and Mona's father who acts as the film's main antagonist. He stubbornly sticks to a doctrinal method of teaching, putting him at odds with Rancho. In the end, he is shown to have changed his doctrinal methods of teaching.
Kareena Kapoor as Pia Sahastrabuddhe, Virus' younger daughter, an intelligent medical student. Despite her father's disapproval, she and Rancho fall in love.
Omi Vaidya as Chatur Ramalingam, a Ugandan-Indian educated in Tamil-speaking Pondicherry who has little knowledge of Hindi, and Rancho's rival whose habit of being flatulent due to the consumption of certain pills claimed to enhance his memorization earns him the nickname "Silencer"; in the present story, he is vice-president of Rockledge Corporation who discovers his success being overshadowed by Phunsukh Wangdu a.k.a. Rancho at the end of the film. Baradwaj Rangan wrote that Chatur being a Tamil from Uganda makes him "twice removed from the North Indians around him – a stranger to the nation as well as the national language."
Rahul Kumar as Manmohan a.k.a. Millimetre, an adolescent boy who earns a small living by doing errands for students such as laundry, finishing assignments and getting groceries. Rancho persuades him to buy a school uniform and sneak into school to gain an education.
Dushyant Wagh as an adult Manmohan a.k.a. Centimetre, Rancho/Phunsukh Wangdu's assistant in Ladakh.
Mona Singh as Mona Sahastrabuddhe, Pia's elder sister and Virus's first daughter
Parikshit Sahni as Mr. Qureshi (nicknamed Hitler Qureshi by Rancho and Raju), Farhan's father, a strict but loving parent who eventually wants his son to be happy.
Farida Dadi as Mrs. Qureshi, Farhan's mother, a loving and caring parent.
Amardeep Jha as Mrs. Rastogi (nicknamed Mother Teresa by Rancho and Farhan), Raju's mother, a retired schoolteacher and dedicated mother.
Mukund Bhatt as Mr. Rastogi, Raju's paralyzed father who used to work as a postman.
Rajendra Patwardhan as Govind, Viru's personal assistant.
Javed Jaffrey as the real Ranchoddas Shyamaldas Chanchad. It is from him that Raju and Farhan learn the truth: Chanchad's father sponsored an orphaned servant boy called 'Chhote', who had demonstrated his intelligence and love of learning, to earn a degree in the real Ranchoddas's name, while he was in London. He appreciates what Chhote did for him, and tells Raju and Farhan where to find him. (Cameo appearance)
Arun Bali in a special appearance as Shyamaldas Chanchad, the father of the real Ranchhoddas Shyamaldas Chanchad and Chhote's foster-father
Ali Fazal in a cameo appearance as Joy Lobo, a student with a passion for machines. After Virus tells him that he will not graduate, Rancho, Farhan and Raju helps him in his project but Joy dies by suicide
Akhil Mishra as Librarian Dubey.
Rohitash Gaud as the real Ranchoddas's servant.
Achyut Potdar as Machine Class Professor
Madhav Vaze as Mr. Karan Lobo, Joy Lobo's father.
Rahul puri as Suhas Tandon, Pia's ex-fiancé, who cares only about money and ostentation. He is called a "fool" by Rancho, as he studied engineering but later completed MBA.
Jayant Kripalani as a company head who conducts Raju's job interview.
Atul Tiwari as R.D. Tripathi, Education Minister in Auditorium during Silencer's speech.
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