The defending Canadian men's curling champions scored two points in the seventh end and wrapped up the win with two more in the ninth after Jamie Murphy and his Halifax rink held Gushue to task for much of the game.
Gushue maintained first place in Pool A over Alberta and the wild-card team, tied for second at 4-1.
Northern Ontario's Brad Jacobs, Manitoba's Reid Carruthers and Ontario's John Epping improved to 5-1 atop Pool B with wins in Tuesday's night draw.
Jacobs defeated Quebec 7-3 in nine ends, Epping topped Prince Edward Island 11-4 and Carruthers beat New Brunswick 7-3. Quebec's Mike Fournier and New Brunswick's James Grattan both dropped to 2-4 and P.E.I's Eddie MacKenzie fell to 1-5.
Gushue was the only undefeated skip remaining in Regina after Manitoba and Northern Ontario suffered losses in Tuesday's early draw.
Carruthers suffered his first loss in a 10-5 defeat to Ontario and Jacobs fell 8-4 to host Saskatchewan. Steve Laycock's team opened the scoring with four in the second end and added a three-point fifth end en route to improving its record to 3-2.
"We didn't really have a good command of the ice and the rocks, it was a pretty poor performance personally,'' Northern Ontario vice-skip Ryan Fry said of their loss to Saskatchewan. "Brad was able to rebound with a great game (Tuesday night), so as long as one of us is playing really good we've got a chance at winning.''
With a new format that includes a wild-card team for the first time, Gushue said he altered his approach a little at this Brier.
"I believe we did a little bit, or me personally,'' he said. "I took it a little lighter early on in the week, especially this year with the two Olympic trials and a big push, there's a burnout factor that you have to take into account. From an intensity standpoint, we are starting to ramp it up.''
In other night-draw action, Nunavut (0-6) remained winless with a 10-3 loss to Saskatchewan (4-2), which has won four straight.
"We've been 0-2 at lots of bonspiels and battled back,'' said Saskatchewan third Kirk Muyres. "Now to get that fourth win in a row, we're starting to roll, getting that confidence back, that little bit of swagger and we're going to set ourselves up nice for the championship pool too if we can win (Wednesday).''