The Mets' top prospect struck out nine and allowed a run on five hits over six innings but did not factor into the decision as Double-A Binghamton lost at Portland, 4-3.
Wheeler took a shutout into the sixth before running into some trouble, allowing a single to Juan Carlos Linares and a double to Dan Butler with one out. The Georgia native got Oscar Tejeda to hit a sacrifice fly and fanned Jonathan Hee to end the frame and his night after 81 pitches.
"My fastball was working and that's what helped me out," Wheeler said. "I had command of my fastball tonight and I worked my slider off that. It had good depth to it, there were a lot of swing-throughs and I got a lot of ground balls off it."
The 21-year-old right-hander fared better than he did in his Double-A debut a week ago, when he allowed two runs on four hits and three walks over three innings against Akron.
"I'm pleased, especially after my first outing," he said. "The first outing, I fell behind everybody and my pitch count was up early and I had to come out. It's always nice to go deep into a game so your bullpen doesn't have to work early. Pound the zone and let your pitches do your work and you can go a little deeper."
The nine strikeouts are the most for Wheeler since he was acquired from the Giants on July 28, 2011 in the deal for outfielder Carlos Beltran. He fanned a career-high 12 batters on May 29, 2011 for Class A Advanced San Jose.
Wheeler has a very simple goal for his first full season in the organization.
"Just commanding my off-speed pitches a little better," he said. "I worked hard on that this offseason and when I have my fastball like it is, it can make my off-speed stuff better."
Red Sox No. 2 prospect Bryce Brentz came off the bench in the fourth inning and slugged his first Double-A homer, helping Portland erase an early 3-0 deficit.
Linares, Boston's No. 20 prospect, capped the Sea Dogs' comeback in the eighth with a two-run homer off reliever Erik Turgeon.