DeLuca’s strikeout on Friday night came after Tampa Bay’s Liam Hicks had grounded into an apparent game-ending double play that was overturned after a video review.
Replays determined that Brewers shortstop Cooper Pratt’s right foot was slightly off the bag when he reached to catch a high throw from second baseman Brice Turang.
Jacob Misiorowski allowed one run over five innings to earn the win.
Christian Yelich hit an RBI triple to spark a two-run rally in the first inning that put the Brewers ahead for good and delighted a sellout crowd revelling in Milwaukee’s first World Series game since 1982.
Jackson Chourio and William Contreras provided two hits each, and Contreras also threw out two potential base stealers.
This marks the first World Series featuring two potential first-time champions since 1980, when the Philadelphia Phillies beat the Kansas City Royals in six games.
The only other major league teams without a World Series title are the Colorado Rockies, San Diego Padres and Seattle Mariners.
The game one winner has gone on to win the World Series 62.8 percent of the time.
Tampa Bay trailed 3-1 and hadn’t put a runner on since the sixth inning until it mounted its comeback try in the ninth.
Jonathan Aranda and Chandler Simpson hit consecutive one-out singles off Megill.
A double steal involving pinch-runner Jorge Mateo and Simpson put the potential tying run in scoring position with Rays slugger Junior Caminero at the plate.
Caminero walked on a 3-2 pitch in the dirt to load the bases.
Hicks hit a grounder to the right side, and Turang ranged well to his left to field the ball before throwing to Pratt to start what initially was ruled a game-ending double play.
But a replay review determined Pratt’s right foot came off the bag as he caught Turang’s throw.
Hicks was still out at first, but the Rays now had runners at second and third with the score 3-2.
Megill finally closed the deal as DeLuca struck out swinging.
By sweeping the two-time defending World Series champion Los Angeles Dodgers in the National League Championship Series, the Brewers had time to set up their rotation the way they wanted by handing the Game 1 start to Misiorowski, the hard-throwing NL Cy Young Award favourite.
Misiorowski opened the game by throwing the fastest pitch ever delivered in a World Series game, a 103.5 mph ball to Yandy Díaz.
The right-hander ended up allowing only one run over five innings with a season-low three strikeouts. (AP)