The English striker, who joined the Reds from Tottenham in late February, scored twice inside the first 25 minutes at CenturyLink Field before Clint Dempsey pulled one back for the Sounders.
Defoe's first MLS goal came in the 17th minute when he was the recipient of a lovely through ball from Jonathan Osorio which allowed him to beat two defenders to the ball before slotting first-time past former TFC keeper Stefan Frei.
Toronto then found themselves two goals ahead in the 24th minute when Defoe raced onto a poor backpass from Marco Pappa to advance to the top of the area and fire beyond Frei for his second.
Obafemi Martins set up Dempsey in the 68th minute for the ex-Fulham and Spurs ace to rifle past Julio Cesar in a who's who of former Premier League stars which eventually had Toronto come out on top for a season-opening victory in their first fixture of the 2014 campaign.
Seattle's loss comes after their 1-0 opening weekend win over reigning MLS Cup champions Sporting Kansas City which sees them fall to fifth on the Western Conference while TFC went fourth in the East.
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