E. Sreedharan was born on 12 June 1932 in Karukaputhur in the present-day Palakkad district of Kerala state.His primary education was from Government Lower Primary School Chathannur near Pattambi in Palakkad district. He completed his education at the Basel Evangelical Mission Higher Secondary School and then went to the Victoria College in Palghat. He later-on completed his Civil Engineering degree from the Government Engineering College, Kakinada, Andhra Pradesh, presently known as JNTUK.

For a short period, Sreedharan worked as a lecturer in Civil engineering at the Government Polytechnic, Kozhikode and a year at the Bombay Port Trust as an apprentice. He subsequently joined the Indian Engineering Service (IES), after clearing the Engineering Services Exam in 1953 conducted by the UPSC. His first assignment was in the Southern Railway as a Probationary Assistant Engineer in December 1954.

In December 1964, a cyclone washed away parts of Pamban Bridge that connected Rameswaram to mainland Tamil Nadu. The Railways set a target of six months for the bridge to be repaired while Sreedharan's boss, under whose jurisdiction the bridge came, reduced it to three months. Sreedharan was put in-charge of the execution and he restored the bridge in just 46 days. The Railway minister's Award was given to him in recognition of this achievement.

In 1970, as the deputy chief Engineer, he was put in charge of the implementation, planning and design of the Calcutta metro, the first ever metro in India. Sreedharan not only completed this much heralded project but also laid down the foundation of modern infrastructure engineering in India. He was taken off this post in 1975.

When Sreedharan joined the Cochin Shipyard in October 1979, it was undergoing a phase of unproductivity. The production of its first ship MV Rani Padmini had been delayed for a long period. When Sreedharan took over, he turned the fortunes of the shipyard around and made sure its first ship was built while he was its chairman and managing Director (CMD). In 1981, under Sreedharan's leadership, the shipyard launched its first ship, the MV Rani Padmini.

He was promoted as general manager, Western Railway in July 1987, and in July 1989 elevated to the post of Member Engineering, Railway Board and ex-officio Secretary to the Government of India. On his retirement in June 1990, the Government made it clear it still needed his services and he was appointed the CMD of Konkan Railway on contract in 1990 by the then railway minister, George Fernandes. Under his stewardship, the company executed its mandate in seven years. The project was unique in many respects. It was the first major project in India to be undertaken on a BOT (Build-Operate-Transfer) basis; the organisation structure was different from that of a typical Indian Railway set-up; the project had 93 tunnels along a length of 82 km and involved tunnelling through soft soil. The total project covered 760 km and had over 150 bridges. That a public sector project could be completed without significant cost and time overruns was considered an achievement by many. Konkan Railway has been covered in the Extreme Railways program by Chris Tarrant as one of the most difficult railway project to have been constructed in the world.

He was made the managing Director of Delhi Metro Rail Corporation by then Delhi Chief Minister Sahib Singh Verma and by mid 1997 all the scheduled sections were completed by their target date or before, and within their respective budgets. Sreedharan was given the sobriquet of Metro Man by the media for his grand success in executing the completion of the Delhi Metro. His stint in the Delhi Metro has been considered so successful and crucial to India that in 2005, he was awarded the Chevalier de la Légion d'honneur (Knight of the Legion of Honour) by the government of France, and the Padma Vibhushan by the government of India in 2008. There were also demands by prominent political figures that Sreedharan be awarded the Bharat Ratna, the most prestigious civilian award in India. He was particularly known for isolating his projects from political pressures and influences and winning political commitments for fast execution of projects. He had announced that he would retire by the end of 2005, but his tenure was further extended to oversee the completion of the second phase of Delhi Metro. After 16 years of Service with the Delhi Metro, Sreedharan retired from Service on 31 December 2011.

After his retirement from DMRC, Sreedharan has been appointed as Principal Advisor of the Kochi Metro Rail Project. Initially, the project faced hurdles when a controversy broke out with the government announcing a global tender process for Kochi Metro, rather than letting DMRC handle the consultancy and project execution as Sreedharan and DMRC had initially asked for. Vested interests in the government have been alleged in this decision. However, several political parties came out in opposition of the move, and backed Sreedharan's decision in enforcing DMRC's role in the Kochi Metro, after which the government reversed its stance. Kochi metro was finally unveiled on 17 June 2017 amidst much celebrations. The unveiling of the metro was considered a landmark event in India in terms of completion time, control systems used and initiatives such as employing transgender people, vertical gardening, respecting migrant laborers, and use of solar power.