It was Hull's first home defeat under manager Marco Silva, who rued costly lapses in concentration but put on a brave face ahead of what will be a tense home straight.
"It's disappointing," Silva told the BBC after his side missed a barrage of chances against the visitors, who completed a league double over Hull after winning the reverse fixture 3-0.
"We had chances to score in many moments of the game. When you don't do this you lose focus and we conceded two from set pieces. Ultimately there was big tension in some of the team."
Sunderland keeper Jordan Pickford enjoyed a superb afternoon as he pulled off a string of excellent saves, denying Sam Lucas, Lazar Markovic and Abel Hernandez either side of Jones's 69th-minute opener.
The right back silenced the home fans with a diving header which went in off the far post after central defender John O'Shea flicked a George Honeyman corner into his path.
Pickford kept Sunderland in the driving seat as he palmed away a Hernandez sitter after Baye Oumar Niasse also missed a gilt-edged chance, driving his shot wide from 14 metres.
With the clock running down, Defoe struck the killer blow as he bundled home the second goal in stoppage time, although television replays showed he was offside when an inviting cross from the right was delivered into his path.
"Now is the moment to rest and analyse," said Silva after seeing his side slide perilously close to relegation.
"We didn't get what we wanted from the match but we have two more games. It's an important moment for us."
Hull visit fellow strugglers Crystal Palace next weekend before hosting second-placed Tottenham Hotspur in their final game of the season.
(Writing by Zoran Milosavljevic; Editing by Clare Fallon)
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