The win edged the Rays ahead of Cleveland by one-half game for the top spot in the American League wild-card race and lessened Baltimore's chances of reaching the playoffs.
Desmond Jennings doubled with one out in the Tampa Bay 18th and Escobar walked. De Jesus took a called strike but then lined a pitch over the head of second baseman Brian Roberts. Jennings scored standing up as the throw from the outfield was slightly up the third-base line.
That saddled Bud Norris (10-12) with the loss as he allowed three hits and two walks in 2 1/3 innings of relief. The Ray's Jeremy Hellickson (12-9), with 2 1/3 innings of one-hit relief got the win. They were the last of a major-league record 21 pitchers used in the game.
DeJesus' game-winning hit left him 4-for-8 in the game while Zobrist went 3-for-8. Both players knocked in two runs over the course of the 6-hour, 54-minute contest that ended after 2 a.m. It was the longest game in either team's history.
Tampa Bay led 3-0 after two innings with DeJesus and Zobrist opening the first with back-to-back doubles and Zobrist scored on an error. DeJesus delivered a sacrifice fly in the second.
The Orioles took a 4-3 lead with rallies in three consecutive innings. Adam Jones knocked in Michael Morse with a single in the fifth, Matt Wieters scored on a groundout in the sixth and Jones had an RBI double and Danny Valencia a sacrifice fly in the sixth.
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Michael Sam cut from the Dallas Cowboys