Sheffield Wednesday striker Gary Madine took his tally to 14 goals this season as Notts County lost for the first time under Keith Curle.
Michail Antonio beat two players to cross for Ryan Lowe to tap home inside the six-yard box to put the Owls ahead.
Lewis Buxton's throw set up Madine to fire into the bottom left-hand corner.
Notts pulled a goal back as substitute Lloyd Sam, got the final touch to an Alan Judge free kick.
The Owls, who completed their first double over Notts for 99 years, stay third but move level on points with rivals Sheffield United, who could only draw 1-1 with Tranmere.
Wednesday stretch their unbeaten run under new manager Dave Jones to four matches and have now won three in succession.
Notts stay just inside the play-off places in sixth but Curle tasted defeat for the first time in seven matches since taking over from Martin Allen in mid-February.
VIEWS FROM THE DRESSING ROOM
Notts County manager Keith Curle told BBC Radio Nottingham:
"Being honest, I think that's the best unit that we've played against. I thought they were big, strong, a good squad of players, able to bring good players off the bench as well.
"They'd got a game plan, they stick to it. They got about and stopped us from playing the way we wanted to play at times.
"Saying that, I don't think we asked them enough questions, which was slightly disappointing but there was a big effort from the players and I thought we gave a very good team a run for their money."
Sheffield Wednesday manager Dave Jones told BBC Radio Sheffield:
"I think we contained them and then in the second half I just opened it up a little bit and gave them licence to get into areas I felt we could do them more harm
"I thought we were patient, we made the right decisions and we put the ball in the areas that they were going to get frustrated.
"[On newspaper speculation linking the Owls with Robbie Fowler] Unless he's trying to get hold of me for a game of golf I've no idea, I've not spoken to Robbie."