Justice Venkatachalaiah began practicing general in 1951. He was appointed as the Permanent Judge of High Court of Karnataka from 6th November 1975. He was appointed Judge of the Supreme Court of India from 5th October 1987. He was appointed by Shankar Dayal Sharma as the 25th Chief Justice of India from 12th February 1993 to 24th October 1994. He was preceded by L. M. Sharma and succeeded by A. M. Ahmadi. Justice Venkatachalaiah was the 2nd Chairman National Human Rights Commission (26th November 1996 - 24th October 1999). He also served as the Chairman of National Human Rights Commission (1996-1998). He also worked on the anti-corruption and human rights issues.

Justice Venkatachalaiah Commission, known as the National Commission, was established to find the working of the Constitution (NCRWC). This was set up by a resolution of the NDA Government of India led by Atal Bihari Vajpayee (22nd February 2000). The main objective was to make possible amendments to the Constitution of India. The report was submitted in 2002.

In 2003, Justice Venkatachalaiah supported the launching of the Initiatives of Change Centre for Indian Governance. He was on the Advisory Board of Foundation for Restoration of National Values. This is a society established in 2008 that was meant to restore as the national and cultural values of India.

Presently, Justice Venkatachalaiah serves as the Chancellor of Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam (Deemed University), which is a Modern Gurukula where the teacher-student interaction occurs in the process of Integral Education. The dimensions include Intellectual, Cultural, Physical, Service, and Devotional.

Justice Venkatachalaiah is the Chairman of the Advisory Board of Prayoga.