Hertha, who announced a 127 million euro investment in June in their effort to eventually compete for silverware, barely had any chances until they struck twice in three minutes late in the first half.
Peter Pekarik was left unmarked at the far post and tapped in for the lead in the 42nd minute.
Forward Dodi Lukebakio then stunned the hosts – and 8,500 home fans allowed to attend the match – firing in a second on the stroke of halftime.
With Werder forced to go forward, Hertha found the space to score again with Matheus Cunha wrongfooting keeper Jiri Pavlenka with a low shot before newcomer Jhon Cordoba added his first goal for the club in the 90th minute.
Davie Selke had earlier cut the deficit in the 68th with a close-range header against his former club.
Freiburg were made to sweat against VfB Stuttgart, eventually edging past them 3-2 having gone 3-0 up only to see their opponents score twice late in the game.
Andrej Kramaric scored a hat-trick to hand Hoffenheim a 3-2 win at Cologne, who had equalised twice.
Bayern kicked off their season with an 8-0 demolition of Schalke 04 on Friday. Borussia Dortmund, last season’s runners-up, host Borussia Moenchengladbach.