John Sutton put the home side in front from the spot after Paul Mayo brought down Martin Bullock in the box and was sent off.
Notts County scored an unlikely equaliser through Richard Butcher, but Scott McGleish and Matt Bloomfield fired back to earn Wycombe a deserved win.
In a lively first half Wycombe almost took an early lead after a mazy run from Bullock which saw the ball fall to McGleish on the edge of the box, but his curling effort hit the underside of the bar.
But for all Wycombe's dominance they almost went into the break behind when Hector Sam thundered the bar with a powerful header from Neil Mackenzie's cross.
The game burst into life minutes after the interval when Bullock burst through on goal, the quick winger was too quick for last man Mayo and was tripped inside the penalty area. Mayo was given his marching orders and John Sutton sent the keeper the wrong way to give his side a 48th minute lead.
Russell Martin's 25-yard shot then hit the post on 55 minutes for Wycombe.
County had a glorious chance to level on 63 minutes when home keeper Frank Fielding's punch fell straight to Butcher, and with an empty goal gaping David McCracken put in a heroic block.
He made amends for that miss on 68 minutes though, Hector Sam beat the offside trap and pulled back for Butcher who hit side-footed home from 10 yards.
But three minutes later McGleish got on the end of a Sutton flick, and hit an early shot from 20 yards that found the corner of the net.
Substitute Bloomfield then finished the game off when his perfectly timed run was found by McGleish, and he hit the net from eight yards.