The former Queens Park Rangers centre back replaces Paul Mariner, who took over 10 games into the disastrous 2012 season for the MLS club.
Fran O'Leary also joins as assistant coach and director of player recruitment.
Beset by injuries and lack of depth, Toronto lurched to a franchise-worst 5-21-8 record.
The 35-year-old Nelson played for Toronto president and GM Kevin Payne at D.C. United. He also spent time in England with Blackburn Rovers and Tottenham.
Nelson becomes Toronto's eighth coach in six years.
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