DeGroote was born in Belgium to Flemish parents and immigrated to Canada with his parents when he was 14 years old. He left school in Grade 9 to help his family by working in the tobacco fields near Tillsonburg, Ontario.
In 1959 he purchased Laidlaw Transport Ltd., a small trucking company based in Hagersville, Ontario. Under his direction, Laidlaw expanded past trucking by entering the solid waste and school bus industries. By the mid 1970s Laidlaw was a large and successful business, and DeGroote had personally become wealthy enough that he was able to purchase the Hamilton Tiger-Cats of the Canadian Football League. He was the last owner of the Tiger Cats to make profit off of the team.
In March 1988, DeGroote sold his Laidlaw shares to Canadian Pacific; in return, he received a combination of cash and CP shares worth $499 million.
In 1990, he retired to Bermuda. However, controversy followed him after his departure: in December 1990, he resigned as a Laidlaw director, and in August 1992, Laidlaw paid $7.65 million to settle a class action lawsuit which had alleged that Laidlaw's corporate officers had "misrepresented the financial condition of Laidlaw." DeGroote also paid $23 million to the Ontario Securities Commission to settle a claim regarding insider trading of Laidlaw stock.
Though still residing in Bermuda, DeGroote has been involved in a number of business ventures since his retirement, such as Republic Waste, AutoNation, NRX Global Inc and Century Business Services.
In 1990, DeGroote was made an Officer of the Order of Canada.
In 1992, he made a major donation to McMaster University which funded the construction of a new business school, which was subsequently renamed the Michael G. DeGroote School of Business. The same year, he received an honorary degree from McMaster.
In 2003, he donated $105 million to McMaster, which funded a number of medical research centres as well as a building, the Michael G. DeGroote Centre for Learning and Discovery (commonly abbreviated as MDCL to avoid confusion with the DeGroote School of Business). In addition, the McMaster School of Medicine was renamed to the Michael G. DeGroote School of Medicine at McMaster in 2004.
In 2009, he donated $10.5 million to Hillfield Strathallan College, which added to existing funds for the planned campus restructuring and the new Senior School building which will bear his name. DeGroote was made an honorary member of Hillfield Strathallan's 2009 graduating class.
In 2014, at the McMaster University Michael G. DeGroote School of Medicine graduation ceremony, Michael took the stage to announce a gift of $50 million. The gift will support increased focus on national and international health leadership, including developing stronger ties with McMaster's DeGroote School of Business as well as partnerships that focus on biomedical advances. Additionally, a new fund will be created to seed the very best medical research within the Faculty of Health Sciences.
In 2011 Michael G. DeGroote invested in a Caribbean business venture which brought him in contact with criminal individuals. A 2015 cbs documentary features a secret recording where a plan to murder the Carbone brothers was discussed by DeGroote.