In his latest loss, he could only blame himself.
Guthrie fell apart in the sixth inning, yielding six consecutive two-out hits in a 6-5 loss to the Detroit Tigers on Saturday night.
Guthrie (5-16) was handed a 5-0 lead in the second, a rarity in a season in which he received 3.58 runs per game, the ninth-lowest run support in the AL.
He took a two-hitter and a 5-1 lead into the sixth, and then it all came apart. He retired the first two batters before Magglio Ordonez doubled and Miguel Cabrera hit the next pitch over the right-field wall. Victor Martinez and Jhonny Peralta followed with singles, and Alex Avila hit a ground-rule double on a 3-0 pitch to cut the deficit to 5-4.
Ryan Raburn concluded the onslaught and chased Guthrie by grounding a two-run single up the middle.
"Early in the game he was getting ahead and getting us to chase pitches that he wanted," Raburn said of Guthrie. "That inning we more or less made him throw the pitches we wanted to hit and got ahead in the count. I was able to hit a mistake."
Guthrie was exceptional for 5 2-3 innings. Then he wasn't.
"Just centered a lot of balls," Orioles manager Buck Showalter said.
"I thought a portion of them were executed pretty well and they just were able to put a good swing on them anyway," Guthrie said. "But certainly there were some that caught a lot of the plate as well."
In absorbing his major-league leading 16th defeat, Guthrie failed to go seven innings for the first time in six starts since July 14.
Rookie Blake Davis hit his first major league homer and Vladimir Guerrero also connected for the Orioles, who have lost nine of 11. By dropping the first two games of the three-game set, Baltimore is 0-12-1 in its last 13 series since June 26.
Adam Jones led off the Baltimore second with a single and Guerrero followed with his 10th home run, the first since July 30. Matt Wieters singled and advanced on an error by Raburn, who fielded a grounder at second base and made an errant flip to shortstop Peralta with his glove.
One out later, Davis hit a three-run, opposite-field drive that barely cleared the glove of leaping left fielder Andy Dirks. The ball bounced back onto the field from beyond the wall, and the umpires reviewed the hit on a replay before deeming it a home run.
"I had no idea," Davis said. "I just saw the guy jump up and it looked like it hit off his glove and bounced back so I kept running around the bases. I didn't know until some guys checked-in on the video and they said it was for sure a home run."
It was his first long ball in 53 at-bats and the highlight of Baltimore's first five-run inning since July 18.
"It's pretty awesome," Davis said.
Four innings later, however, the Tigers put together a string of six consecutive hits in what would turn out to be their biggest comeback victory of the season.
Detroit's previous biggest rally-to-win performance was from three runs down. This victory enabled the Tigers to maintain their three-game edge over Cleveland in the AL Central.
"The guys didn't quit. I'm proud of them," Leyland said. "This could have been a tough game for them."
Cabrera finished with three RBIs for the Tigers, whose last eight wins have all been by one run — a club record.
Max Scherzer (12-7) got the victory despite yielding five runs in the second inning. The right-hander gave up four earned runs and seven hits over seven innings, striking out a season-high 10 and walking none.
Scherzer finished his outing by striking out J.J. Hardy with two outs and two on. Walking off the mound after his 120th pitch, he emphatically pounded his fist into his glove.
The 12 wins matches his career high for a single season, set last year.
NOTES: Detroit RHP Al Alburquerque was released from the hospital with a concussion after being struck by a line drive during batting practice on Friday. He was to be driven back to Detroit on Sunday because doctors advised him not to fly. ... Former Baltimore SS Mike Bordick was formally inducted into the Orioles Hall of Fame in a pregame ceremony. ... Ordonez is 7 for 13 lifetime against Guthrie. ... Detroit will send Doug Fister (4-12) to the mound Sunday looking for a sweep. The Orioles will counter with Jo-Jo Reyes, making his second start for Baltimore since being acquired on waivers from Toronto.