David Edwards scored early on and Sylvan Ebanks-Blake added a second for the visitors with a stunning overhead kick as they claimed all three points after a winless run that had stretched to 12 games, with Saunders being in charge of nine of them.
Wolves are now out of the drop zone, while Kenny Jackett’s Lions have now lost seven of their last eight and have suffered four defeats in a row at the Den.
Saunders’ men took control of the game after just nine minutes. Stephen Ward broke down the left and crossed for Ebanks-Blake at the back-post, who controlled nicely before setting-up Edwards in the middle to cushion a volley into the net.
Millwall’s nightmare start continued as striker Benik Afobe was unable to continue due to injury and was replaced by former Wolves player Andy Keogh.
And they almost fell a further goal behind. Bakary Sako was fouled by Chris Taylor down the left and Karl Henry’s delivery was partially cleared by Danny Shittu, but the ball fell for Edwards whose volley was well blocked by Shane Lowry.
Wolves were comfortable throughout the opening half-hour, with the home side unable to put them under any sustained pressure. Their frustrations boiled over with a number of heated exchanges. Keogh and ex-teammate Kaspars Gorkss clashed, as did Ebanks-Blake and Adam Smith, before Smith fouled Bakary Sako.
Two minutes later, Sako became the first man into referee Mick Russell’s book as he returned the favour with a late challenge on Smith.
From Josh Wright’s resulting free-kick, Taylor headed Millwall’s first shot on target but Carl Ikeme handled comfortably. A second soon followed and this time Wright’s cross found Lowry but Ikeme held well again.
John Marquis required treatment on a shoulder injury before the break and did not come out for the second half, with Nathan Tyson coming on in his place.
Millwall offered the bigger threat after the break and went within inches of an equaliser in the 52nd minute. Taylor did well down the right and his cross was just too far in front of Keogh at the back post.
But just as it looked as if the home side would grab an equaliser, Ebanks-Blake struck in spectacular fashion to put the game to bed. The former Manchester United striker’s initial effort was blocked by Mark Beevers but after Jamie O’Hara headed the ball back into the middle, the striker acrobatically found the back of the net from 12 yards.
Millwall never threatened a way back into the game, leaving Saunders celebrating success for the first time since he left Doncaster.