Based on the true story of a hotel manager who saved hundreds of lives during the country's 1994 genocide, Hotel Rwanda won the People's Choice award on Sunday - voted by regular moviegoers at the 9-18 September festival.
The prize is often an indicator of future Academy Award nominations, with past recipients including Oscar winners American Beauty, Life is Beautiful, Shine and Chariots of Fire.
Omagh, which tells the story of the relatives of victims of the 1998 bombing in Northern Ireland, won the event's Discovery award.
The prize is chosen by the hundreds of journalists who attend the Toronto festival, which ranks with Cannes, Venice, Berlin and Sundance as among the world's most influential.
"We're enormously pleased that a subtle political cast that we chose to give to this festival in this very important year has been reflected in the awards," said festival co-director Noah Cowan.
Other prize-winners included In My Father's Den, a New Zealand film about a prize-winning war journalist who returns to his remote hometown. It won the Fipresci prize given by a jury to emerging filmmakers.
Canadian film prizes went to comedy It's All Gone Pete Tong and French-language horror film White Skin.
The awards brought to an end a politically-charged edition of the festival, which screened 328 films over 10 days.