The reigning German champions made yet another important step to defending their crown as they made short work of the Oh-Fives, led by coach Thomas Tuchel
Jakub 'Kuba' Blaszczykowski opened the scoring in the first half for BVB, who dominated the match for large portions, but could not make the most of the chances that came their way.
This came back to haunt them when Mohamed Zidan netted against his former club in the second period. Shinji Kagawa, however, had the final say as he struck the winner shortly after to claim the three points for BVB.
Dortmund showed they meant business right from the start as they created their first clear-cut chance only nine minutes into the game. Some good interplay between Lukas Piszczek and Shinji Kagawa resulted in the defender firing in a cross, which Kevin Grosskreutz just could not stab in.
BVB had a penalty shout turned down in the 24th minute, but it did not matter as two minutes later Kuba popped up with the opener. It took two defenders to stop Kagawa, but to no avail as the ball fell to the Polish international, who powered a thunderbolt in the top left corner.
Dortmund continued to aggressively pin Mainz in their own half and looked like scoring with every chance. Some desperate goalkeeping and defending kept the champions at bay, and the hosts withdrew at half-time with a one-goal advantage.
The restart saw BVB continue to press Mainz, who were struggling to cross the half-way line. Lewandowski missed a great chance in the 50th minute, and Kagawa followed suit shortly after.
Out of nowhere, however, Mainz found the equaliser. Some good work from substitute Adam Szalai allowed the Hungary international to slip the ball to former Dortmund striker Zidan, who fired an unstoppable shot which Roman Weidenfeller could only parry into the net.
Before Uli Hoeness & Co. could breathe a sigh of relief far away in Munich, though, Kagawa restored Dortmund's lead with a neat finish. Piszczek stormed down the flank and delivered a superb cross for the Japanese, who finished from close range.
Mainz tried to mount a late comeback in the last minutes of the game, but were ultimately unable to do so as the reigning German champions claimed their first home win against Mainz in almost seven years.
Following Saturday's win, Borussia Dortmund are first in the Bundesliga standings with 55 points, seven clear of Bayern, who lost 2-0 at Leverkusen in the earlier kick-off. Mainz, meanwhile, are 12th with 27. BVB's next league match is in one week away to Augsburg, while Thomas Tuchel's men host Nurnberg on the same day.