Marcel Risse and Andre Schuerrle scored within eight minutes in the second half to secure Mainz the road victory and give Thomas Tuchel's club a perfect 12 points from four rounds.
"We were perfectly prepared and I'm happy that everything worked out," said Risse, who also joked that he wanted to keep up with Schuerrle after the 19-year-old notched his third goal in three appearances as a substitute.
Schuerrle was even more relieved after his transfer to Bayer Leverkusen for next season was announced during the week.
"The transfer did so much to ease my mind," Schuerrle said. "Leverkusen is a dream club for me. And I cannot wait for next season. But the Mainz fans know that I am with the club until the end of the season. And what can be better than beating Bremen 2-0?" Mainz is two points ahead of previous leader Hoffenheim, which needed a goal by Gylfi Thor Sigurdsson to secure a 2-2 draw at Kaiserslautern.
Also, defending champion Bayern Munich was held to a 0-0 draw at home against Cologne, Pavel Pogrebnyak scored a hat trick as Stuttgart routed Borussia Moenchengladbach 7-0, and 2009 champion Wolfsburg beat Hannover 2-0.
After trailing 1-0 at Hoffenheim, Erwin Hoffer scored twice for Kaiserslautern but substitute Gylfi Thor Sigurdsson converted a free kick in the 77th minute to secure the draw.
"It wasn't a good game for us in the second half," Hoffenheim coach Ralf Rangnick said. "If we wanted to win in the second half we would have had to have played much stronger. We can be happy with this point." Kaiserslautern's Christian Tiffert said they were also happy with the draw.
"A lot of people think we can only run and kick the ball.
But we played a great game today," he said. "It was probably a better game than against Bayern." Hoffenheim is second with 10 points while promoted Kaiserslautern has seven for fourth place.
Cologne maintained its record as the only team in the Bundesliga to have never lost at Munich's Allianz Arena, extending its unbeaten string to three draws and one victory.
Bayern Munich has just five points in its worst Bundesliga start in 34 years.
"We need to work on things. We are not 100 percent. It's not an excuse. But we just need to work on it," Bayern goalkeeper Hans Joerg Butt said.
"We need three points pretty soon or else things are going to get close," added Thomas Mueller.
Pogrebnyak opened the scoring for Stuttgart after just two minutes and added two more in the second half as the club followed up on its 3-0 victory over Young Boys in the Europa League by taking its first points in the Bundesliga.
"We have shown in past years that we have a team with a lot of character and we showed that on Thursday. And now we did that again today," Stuttgart captain Matthieu Delpierre said.
On Sunday, last-place Schalke looks for its first points of the season when it hosts Borussia Dortmund, Bayer Leverkusen welcomes Nuremberg, and Hamburg plays at city rival St. Pauli.
