Lewis threw a 22-yard touchdown pass to Johnny Lumpkin and a 46-yarder to Dontae Fleming to extend the Ragin' Cajuns' lead to 28-13 in the third quarter.
Gerald Green's 76-yard touchdown run early in the fourth quarter got the Eagles (1-3, 0-1) within 28-20. Their final possession came with 4:22 to go but the drive died with 44 seconds remaining.
Lewis, who also threw a 48-yard score to Michael Jefferson to tie the game at 7, finished 17 of 28 for 249 yards for the Ragin' Cajuns (3-1, 1-0). Emani Bailey had Louisiana-Lafayette's other touchdown on a 3-yard run for a 14-7 lead.
Green rushed for three touchdowns and a career-high 186 yards on 18 carries for the Eagles. Justin Tomlin threw for 175 yards with an interception.
More AP college football: https://apnews.com/hub/college-football and https://twitter.com/AP—Top25. Sign up for the AP’s college football newsletter: https://apnews.com/cfbtop25