Koepka, who has not finished outside the top two in his last four majors, battled to a four-under-par 67 in the third round on Saturday to reach nine-under for the tournament, while Lowry delighted the home fans by powering to a 63.
"Very frustrating. Disappointed. But thankfully it's going to blow tomorrow," said Koepka.
"I need it. Being, what, seven back. Here you need some wind, you need some rain. You need anything that can kind of go your way.
"And that's got to be an advantage. Especially the way I'm striking the ball. I've struck it so good. If it's going to be windy, you need to be able to strike it good, control your flight, and figure out where you want the ball to end up."
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The four-time major winner knows how difficult it can be to hold onto a lead in the final round, after seeing his own seven-stroke advantage briefly whittled down to one by Dustin Johnson in May's PGA Championship at Bethpage Black before winning by two.
Koepka was also quick to remember Lowry's collapse at the 2016 US Open, when he took a four-shot lead into the fourth round, only to struggle to a 76 and finish three behind Johnson.
"The last time Shane had the lead at Oakmont we saw that," said the 29-year-old.
"Bad weather happened at Bethpage. I guess maybe the last 15 holes was very, very windy, especially that back nine.
"In links golf all of a sudden a couple of bad bounces and you never know, or (you're) in a couple of bunkers."
Koepka said he isn't interested in just maintaining his run of high finishes.
Victory on Sunday is his final chance to move above Rory McIlroy at the top of the list of major titles won this decade, and would also put him a Masters green jacket away from becoming the sixth player to complete the career Grand Slam.
"Seven back (not tied-fourth), that's the way I look at it. It's been disappointing.
"It's just not the week that I've expected. But at the same time, there's one more round, so I need to figure it out."