Mazzaro scattered seven hits over 6 1/3 innings of three-run ball, but the two-run home run he served up to Matt LaPorta in the sixth sent the A's to a 3-2 loss against the Indians at Progressive Field.
The 23-year-old righty walked two and struck out five in his 97-pitch outing, which ran Oakland's consecutive quality start streak to 18 games.
"Vin threw the ball OK," A's manager Bob Geren said. "When it's all said and done, it was still a quality start. We just didn't get enough runs today. Three runs allowed at that point of the game is usually a good start.
"Obviously, the pitch to LaPorta wasn't where he wanted it."
Mazzaro wanted the first-pitch two-seam fastball to run away from the right-handed LaPorta. It did no such thing.
"I just left a pitch over the plate," Mazzaro said. "It ran back and he took a good hack at it."
That hack spoiled Oakland's bid for a three-game sweep heading into its weekend series with first-place Texas, which begins on Friday night in Arlington.
Geren was more disappointed in Thursday's loss than the unexecuted sweep.
"When we came into today, we weren't thinking about the last two games," said Geren, whose club trails the Rangers by 8 1/2 games in the AL West standings. "We wanted to win today. We weren't looking at two out of three or three out of three. We would've liked to have gotten this game.
"Anytime you get two out of three, it's good -- but we weren't looking at it any which way going into the game. We just wanted to take this one and go. We just didn't get enough offense to win it today."
Indians starter Justin Masterson was the primary reason for the struggles of Geren's offense. The lanky 25-year-old righty yielded two runs on five hits across six innings of work, firing first-pitch strikes to 19 of the 26 batters he faced.
"With that team," Masterson said of the A's, "you want to get that first pitch in for a strike and get them swinging a little more."
The A's took plenty of swings against Masterson that produced undesired results.
"He had really big movement on his fastball," Geren said. "We had trouble barreling it up. We tried to work our game and steal some bases. We did what we normally do. We just didn't capitalize on any of our opportunities."
Oakland did seize a 1-0 lead in the second. With one down, Masterson unleashed an 0-2 sinker that plunked Mark Ellis. Three batters later, Gabe Gross plated Ellis with a two-out single to left field.
Cleveland used a two-out rally of its own to even the score in the fifth. With two down, Lou Marson worked a walk, stole second base, took third on a Mazzaro wild pitch and scored via Michael Brantley's single to right.
The A's answered right back with a run in the sixth, making Masterson pay for the leadoff walk he issued to Jack Cust. Rajai Davis pinch-ran for Cust at first, swiped second, took third via Ellis' groundout to shortstop and scored on Kevin Kouzmanoff's double to left-center.
But Oakland's bats sputtered after scoring a combined 11 runs in its previous two games. The A's finished 2-for-13 with runners in scoring position and stranded nine.
Their 2-1 lead proved short-lived. LaPorta followed Trevor Crowe's two-out single to left in the sixth with a towering blast over the left-field wall that awarded Cleveland a 3-2 edge.
LaPorta's homer aside, Mazzaro had few criticisms of his performance -- which dropped him to 0-4 with a 3.89 ERA in six starts since July 29.
"Other than that, I thought it went pretty well," Mazzaro said. "They came out swinging. I just wanted to pound the zone and get some easy quick outs. I did that pretty well. I got through the first few innings, but it was a battle.
"I came up a little short. It happens."
The A's worked a pair of walks off Joe Smith in the eighth to put runners on first and second with one out, but Chris Perez fanned Jeff Larish and coaxed Kouzmanoff into a check-swing ground ball to first.
For all of its missed opportunities, Oakland still found itself one swing away from a reversal of fortune in the ninth.
Cliff Pennington's one-out single to right brought the tying run aboard for Coco Crisp. After Pennington stole second, Perez struck out Crisp on a 2-2 fastball and Daric Barton on a 2-2 slider to end the contest.
Minutes removed from Thursday's loss, Geren opted to look toward the future.
"We'll get on the flight and go get 'em tomorrow," Geren said. "We have to be ready."
Still, the sting of a missed opportunity wasn't easily forgotten.
"It's a little disappointing," Mazzaro said. "We took two out of three. That's not bad. It would have been nice to get the sweep, but we'll go get 'em in Texas."
John Barone is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.