Brignac connected on a 3-2 pitch from Sergio Mitre (0-3) and sent it deep into the right field stands, triggering a celebration as the Rays vaulted over the Yankees into first by a half-game.
The clout made a winner of Grant Balfour (2-1), who had tossed a scoreless top of the 11th.
Rays starter David Price threw eight innings of shutout ball, yielding only three hits, walking two and fanning four.
New York's CC Sabathia matched him through eight frames, surrendering only a pair of hits while issuing a two walks and striking out nine.
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