Matches will be played behind closed doors and players and coaches, who have been in quarantine for the past week, must follow stringent hygiene guidelines.
In the highlight of six matches on Saturday, Borussia Dortmund host Schalke 04 in the Ruhr Derby at 1330 GMT, a fixture that would normally attract an 82,000 crowd to Signal Iduna Park.
Professional football returned to western Europe earlier in the day as the second-tier Bundesliga 2 resumed with four matches at 1100 GMT.
South Korean Lee Jae-Sung scored the first league goal in over two months when he gave Holstein Kiel a third-minute lead at Regensburg.
Although Germany has suffered far fewer deaths from coronavirus than other large European countries, it is still too dangerous for crowds to return.
On Sunday, Bayern Munich will resume their quest for an eighth successive Bundesliga title when they play in the capital against Union Berlin.
Bayern were four points clear at the top of the table when the season was suspended in March. An exciting Dortmund team featuring Norwegian striker Erling Braut Haaland and highly-rated English forward Jadon Sancho are in second place.
The German Football League (DFL) made no secret of the fact that several clubs are already in a dire financial situation as a result of the lockdown.
If they are able to complete the nine remaining rounds of matches by June 30, clubs could receive around 300 million euros ($324 million) in money from television contracts.
In order to get the political green light to resume, the DFL has put in place the mass testing of players and staff.
The bus transferring Borussia Dortmund football's team arrives before the German first division Bundesliga football match BVB Borussia Dortmund v Schalke 04 at the Signal Iduna Park on May 16, 2020 in Dortmund, western Germany as the season resumed following a two-month absence due to the novel coronavirus COVID-19 pandemic.
INA FASSBENDER / AFP
The matches themselves will be surrounded by extraordinary measures. Teams will arrive at stadiums in several buses in order to meet social distancing requirements inside the vehicles.
Once play begins, players have been warned not to shake hands or embrace to celebrate goals, while substitutes and coaches on the bench must wear protective masks.
There are also concerns that fans will try to approach stadiums to support their teams from afar. Police in Dortmund have appealed to fans to stay at home.
Clubs in England, Spain and Italy, where leagues are weeks away from returning to action, will be watching to see how the weekend's games go.s