In 1979, David Lepofsky graduated with honours From Osgoode Hall Law School with a Bachelor of Laws. He obtained a Masters of Law from the Harvard Law School in 1982. Since his admission to the Ontario Bar in 1981, he has practiced law in the Ontario Public Service in the areas of constitutional, civil, administrative and most recently, criminal law. Since 1991, he has also served as a part time member of the University of Toronto Faculty of Law, where he teaches an advanced constitutional law seminar on freedom of expression and press.

Since the late 1970s, he has been active in a volunteer capacity, advocating for new laws to protect the rights of persons with disabilities in Canada. In 1980, he appeared before the Joint Committee of the Senate and the House of Commons on the Constitution of Canada, on behalf of the Canadian National Institute for the Blind for an amendment to the proposed Charter of Rights, to guarantee equality rights to persons with disabilities. The efforts of a great many combined to lead Parliament to pass the disability amendment to the Charter.

From 1980 to 1982, he was on the leadership team of a broad disability coalition that successfully advocated for inclusion of protection against discrimination based on disability in the Ontario Human Rights Code.

From 1994 to 2005, he led the Ontarians with Disabilities Act Committee. That coalition successfully campaigned for ten years to win passage of two new Ontario laws to make Ontario fully accessible to persons with disabilities, the Ontarians with Disabilities Act 2001 and the Accessibility for Ontarians with Disabilities Act 2005.  Since then, he has helped in efforts to get that law effectively implemented. As of late February, 2009, David became the chair of the Accessibility for Ontarians with Disabilities Act Alliance.

Starting in 1994, he campaigned to get the Toronto Transit Commission to announce all subway stops, and later all bus stops, for the benefit of passengers with vision loss. Between 2001 and 2007 he fought two cases against TTC. In 2005, the Human Rights Tribunal ordered TTC to consistently announce all subway stops (Lepofsky v. TTC #1). In 2007, the Human Rights Tribunal ordered TTC to announce all bus and streetcar stops. (Lepofsky v TTC #2)  

Awards include investiture in the Order of Canada (1995), the Order of Ontario (2007), and the Terry Fox Hall of Fame (2003), honorary doctorates from Queen's University and the University of Western Ontario, and awards from other organizations including e.g. the City of Toronto, the Law Society of Upper Canada, the Ontario Bar Association Public Lawyers Section, the Advocates Society, the Ontario Crown Attorneys Association, the Ontario March of Dimes and Community Living Ontario.