The former Toronto FC striker stretched out his right leg in the six-yard box to knock in a low cross from Patrick van Aanholt in the 34th minute. It was his 125th goal in the English Premier League.
The goal gave Sunderland a 2-0 lead before 44,022 at the Stadium of Light.
It was Defoe's first Premier League goal in 385 days — he scored 11 in 19 games in an injury-interrupted 2014 MLS season in Toronto — and moved him into a tie with Nicolas Anelka for 13th place in the all-time Premier League scoring list.
Defoe, who almost scored again in the 47th minute, was substituted in the 75th minute to a standing ovation from home fans.
The England striker left Toronto earlier this month in a swap that sent U.S. international forward Jozy Altidore to the MLS team.