Klaas Jan Huntelaar was the first player to beat Fabian Giefer in this campaign in the 13th minute and Joel Matip made it two for the Royal Blues soon after.
However, a Dani Schahin brace in the second half maintained Fortuna's unbeaten record and took them level on points with fourth-placed Hannover, who Schalke climb above thanks to the point
Dusseldorf's defensive resolve this season had been their biggest strength, and they placed the emphasis on this aspect of their game again, sitting deep from the outset.
But Schalke soon found a way through, and unsurprisingly it was the Bundesliga's top scorer from last season, Huntelaar, who put them in front in the 13th minute.
He received a long throw-in from Benedikt Howedes, beat two men and provided a finish out of nowhere to stun Giefer and over 50,000 fans inside the sold-out Dusseldorf Arena.
The crowd fell even more silent seven minutes later when Matip made it two, heading in Christian Fuchs' free-kick.
Andriy Voronin had rarely seen the ball in the first half, but a clear shift in the home side's tactics at the start of the second meant the Ukrainian finally got involved.
And he set up Schahin to bring Fortuna back into the game in the 47th minute with a corner picking out the striker, who headed in his third goal of the season and his first since the opening day.
Goal number four of the campaign arrived in the 77th minute, Schahin's aerial ability again demonstrated to full effect from Tobias Levels' cross.
Fortuna nearly grabbed the lead a minute later when Stefan Reisinger was only just inches away from meeting a low cross at the far post, but the home side decided it was better to defend a point than look for a winner and that is precisely what they did.