After his schooling at Demonstration School, Mysore in 1973, he graduated from the University of Mysore with a bachelor's degree in English literature. During his college years, he developed an interest in travel and motorcycles.

At the age of 25 on 23 September 1982, he rode up Chamundi Hill and sat on a rock, where he claims to have had a spiritual experience. He describes his experience as follows:

In 1983, he conducted his first yoga class with seven participants in Mysore. Over time, he began conducting yoga classes across Karnataka and Hyderabad traveling from class to class on his motorcycle. He lived off the produce of his poultry farm rental and refused payment for the classes. A usual practice of his was to donate the collections received from participants to a local charity on the last day of the class. These initial programs were the basic format on which the Isha Yoga classes were later built.

Jaggi Vasudev established the Isha Foundation, a non religious, non-profit organisation entirely run by volunteers. Isha Yoga Center near Coimbatore was founded in 1993, and hosts a series of programs to heighten self-awareness through Yoga. The foundation works in tandem with International bodies like the Economic and Social Council of the United Nations.

After the establishment of the ashram, Jaggi Vasudev began conducting regular yoga programs at the Isha Yoga Center, including a course for the Indian Hockey team in 1996. In 1997, he began conducting classes in the United States and in 1998, he began conducting yoga classes for life-term prisoners in Tamil Nadu prisons. From 2011, he began conducting programs with large-scale participation of up to 10,000 and 15,000 participants at once. These large-scale programs have been attended by over 75,000 people in total.

In 1994, Jaggi Vasudev conducted the first program in the premises of the newly established Isha Yoga Center, during which he described the Dhyanalinga. The Dhyanalinga is a yogic temple and a space for meditation, the consecration of which, Jaggi Vasudev stated was his life's mission entrusted to him by his guru. In 1996, the stone edifice of the linga was ordered and arrived at the ashram. After three years of work, the Dhyanalinga was completed on 23 June 1999 and opened to the public on 23 November.

Action for Rural Rejuvenation (ARR) is an initiative of the Isha Foundation that aims to improve the overall health and quality of life of the rural poor. ARR was established in 2003 and seeks to benefit 70 million people in 54,000 villages across South India. As of 2010, ARR has reached over 4,200 villages and a population of over 7 million people. He has also been involved with agricultural and farmers' associations to work towards resolving issues faced by Indian farmers.

In 2006, the Foundation entered the Guinness Book of World Records by planting 8,052,587 saplings in 6,284 locations across Tamil Nadu in one day.

In March 2005, construction of the Isha Institute of Inner-sciences (III) in McMinnville, Tennessee, USA was begun and was completed 6 months later. Jaggi Vasudev had decided to establish III as a Center for spiritual growth in the Western Hemisphere. On 7 November 2008, he consecrated the Mahima Hall, a 39,000 square foot, free-standing meditation hall at the III. Mahima Hall is the largest meditation hall in the Western Hemisphere. On 30 January 2010, he consecrated the Linga Bhairavi, a representation of the feminine aspects of the Divine at the Isha Yoga Center.

He is also the founder of Project GreenHands (PGH), a grassroots ecological initiative which was awarded the Indira Gandhi Paryavaran Puraskar, by the Government of India in June 2010. PGH aims to increase the green cover in Tamil Nadu by 10% and has successfully overseen the planting of more than 27 million trees by over 2 million volunteers. In an interview with National Geographic Green magazine, he explained the impetus which led him to establish Project GreenHands: "In the year 1998, certain experts [...] made a prediction, by 2025, 60% of Tamil Nadu will be a desert. [...] I decided to drive across Tamil Nadu and see for myself if this is true. [...] I realized they were completely wrong because it wouldn't go to 2025, it would happen much faster according to me. [...] So from '98 to 2003, 2004, I went about planting trees in people's minds. And since 2004, we [have been] transplanting those trees back to the ground."

In 2012, he initiated the Isha Insight program, which focuses on helping small and medium businesses scale up their Business activities. The program was conducted by Ram Charan with KV Kamath, Grandhi Mallikarjuna Rao, Shankar Annaswamy, Vellayan Subbiah and Pramod Chaudhari also active in the program. In an interview with Forbes magazine, speaking about the motivation behind setting up the program, he said, "While speaking at economic summits and to Leaders in India and outside, I have noticed that the most serious issue people have is a lack of insight into what they are doing, or what they could do. That's how we ended up creating this programme called Insight."

Jaggi Vasudev spoke at the United Nations Millennium World Peace Summit in 2000, the World Economic Forum in 2006, 2007, 2008 and 2009. On 24 June 2013, he conducted a multi-religious session titled, "Interfaith Deliberations on the Universality of Religions" at the Isha Yoga Center, which was attended by representatives of various religions, and coincided with the fourteenth anniversary celebrations of the Dhyanalinga.

Jaggi Vasudev designed the 112-foot statue of Adiyogi, which is located at the Isha Yoga Center. The statue depicts the first yogi. It was inaugurated on Mahashivaratri, 24 February 2017, by the Prime Minister of India, Narendra Modi. The Adiyogi statue depicts Shiva as the first yogi or Adiyogi, and first Guru or Adi Guru, who offered yoga to humanity. The statue was built by Isha Foundation using 20,000 individual iron plates supplied by Steel Authority of India and weighs around 500 tonnes (490 long tons; 550 short tons). The Adiyogi Shiva Statue has been recognized as the "Largest Bust Sculpture" by Guinness World Records. A consecrated Shivalinga called "Yogeshwar Linga" is placed in front of the Adiyogi Shiva statue.