Hughes struck out J.P. Arencibia for the first out, then also fanned Adeiny Hechavarria on a pitch that tipped catcher Russell Martin's glove and sailed to the screen behind home plate for a passed ball.
The right-hander recovered to strike out Anthony Gose swinging and caught Brett Lawrie looking at a called third strike to end the inning.
Hughes joined former teammate A.J. Burnett as the only Bombers hurlers to whiff four batters in an inning. Burnett accomplished the feat on June 24, 2011, against the Rockies, when he struck out Chris Iannetta, Carlos Gonzalez, Chris Nelson and Todd Helton around a wild pitch.