The game-winning points came on a 44-yard field goal by Navy's Joey Bullen as time expired.
Duke falls to 1-3 on the year while Navy improves to 2-2.
Lewis completed 23-of-36 pass attempts for a career-high 428 yards with four touchdowns and one interception. The 428-yard performance marks the seventh-highest single-game total in Duke history while the four scoring tosses match the second-best total. The favorite target for Lewis against the Midshipmen was Eron Riley, who caught six passes for 235 yards and four touchdowns. Riley's day matched the school single-game standard for touchdown receptions while his 235 yards rank as the fifth-highest total in the Duke annuals.
Lewis connected with Riley for touchdown passes covering 76, 35, nine and 69 yards on the afternoon.
Navy got on the scoreboard first with a career-long 46-yard field goal by Matt Harmon with 7:21 remaining in the opening quarter. The scoring drive, which began following a Duke punt, covered 46 yards in nine snaps while eclipsing 4:57 off the clock.
On the next play from scrimmage, Lewis hooked up with Riley for a 76-yard touchdown down the right sideline. The toss matched the ninth-longest pass completion in school history and pushed the Blue Devils ahead, 6-3, at the 7:01 mark of the opening quarter. The Mids responded by driving 69 yards in seven plays for a 44-yard touchdown pass from Kaipo-Noa Kaheaku-Enhada to O.J. Washington. Harmon's point after touchdown vaulted Navy into the lead, 10-6, with 4:14 left in the first period.
Following a 61-yard kickoff return by Jabari Marshall, Lewis found Riley streaking down the left sideline for a 35-yard touchdown. Lewis then completed a two-point conversion pass to Nick Stefanow to push Duke ahead, 14-10, at the 3:55 mark of the first quarter. Navy responded by driving inside the Duke 10 yard line, but Harmon's 26-yard field goal attempt was wide.
The Blue Devils responded with a methodical 10-play, 80-yard scoring drive that Re'quan Boyette capped off with a four-yard touchdown run. Duke again elected to go for two points, and Lewis again found Stefanow open in the end zone to convert for a 22-10 advantage with 12:54 left in the half. Navy then marched 71 yards in eight snaps for a one-yard plunge by Kaheaku-Enhada. Harmon's extra point pulled the Mids to within 22-17 at the 9:03 mark of the second quarter.
The Navy defense then forced a Duke punt, and the Midshipmen took advantage of good field position when Eric Kettani ended a six-play, 60-yard drive with a 10-yard scoring run. Kaheaku-Enhada then found Washington open for the two-point conversion, making the score 25-22 in favor of Navy with 5:36 before halftime. Duke then used an eight-play, 61-yard drive to take a 29-25 lead when Lewis scored from three yards out on the ground and Greg Meyers booted the extra point with 2:31 remaining in the half.
On Navy's next possession, Kaheaku-Enhada was intercepted by Duke's Marcus Jones at the Blue Devil 42 yard line. Lewis took advantage of the turnover by directing a four-play, 58-yard scoring drive that ended when the quarterback's nine-yard fade pass to the back right-hand corner of the end zone was hauled in by Riley. The point after touchdown kick by Meyers pushed Duke's lead to 36-25 with just over one minute left in the period.
The Midshipmen took the opening kickoff of the second half and drove 74 yards in seven plays for a four-yard touchdown run by Kettani, pulling Navy to within 36-32 just over three minutes into the period. The Blue Devils pushed the lead back to 11 points almost immediately, however, when Lewis found Riley for a 69-yard scoring strike on Duke's next possession.
Both offenses went dry until Bullen connected on a 35-yard field goal with 8:07 left in the fourth quarter to trim Duke's lead to 43-35. The field goal capped a 17-play, 62-yard jaunt that took 6:31 off the clock. After a Duke punt, Navy tied the game at 43-43 when quarterback Jarod Bryant caught a touchdown pass and then rushed for the two-point conversion with 3:49 left in the final quarter.
The Blue Devils then drove into Navy territory, but Lewis threw an interception on third down and 21 yards to go, giving the Mids possession at their own 26 yard line with 38 seconds remaining. Bryant led Navy 48 yards on seven plays to set up Bullen's game-winning field goal.
Navy outgained Duke by a 540-506 margin in total yards. The Mids ran 90 plays from scrimmage compared to Duke's 62.
Boyette paced the Blue Devil rushing attack with 42 yards on seven attempts. Jomar Wright caught a game-high seven passes for 89 yards while Boyette had four grabs for 29 yards.
Duke plays the final tilt of its four-game road streak next Saturday, traveling to meet Miami at the Orange Bowl. Kick-off is set for 12 noon.