The cell -- which allegedly included an experienced bomb maker -- was plotting a mass casualty attack on the old town of the western German city, using suicide vests and guns, federal prosecutors say.
There were no indications that the plot, believed ordered by senior ISIS leadership, was in an advanced stage of implementation, the statement said.
The three were apprehended separately Thursday in the states of North Rhine-Westphalia, Brandenburg and Baden-Wurttemberg, the attorney general said in a statement.
The homes of the men -- identified only as Hamza C., 27; Mahood B., 25; and Abd Arahman A. K., 31 -- are being searched for evidence.
German officials have requested extradition of a fourth suspect, a 25-year-old Syrian national named Saleh A., who has been in French custody since February.
Information that the fourth suspect disclosed to French authorities led to the arrests, the statement said.
Attorney General Peter Frank said that Mahood B. was believed to be an ISIS supporter, while the other three were strongly suspected of being members of the terror group.
Abd Arahman A. K. also is suspected of involvement with al Nusra Front, another jihadist group active in Syria.
He is accused of having prepared suicide vests and grenades for the group in the war-torn country in 2013.
Attack plotted in Syria
Prosecutors allege that Saleh A. and Hamza C. joined ISIS in Syria in the spring of 2014, where the terror group's senior leadership commissioned them to attack Dusseldorf.
The plot was to strike Heinrich-Heine-Allee, a street in the city's Altstadt district, using suicide explosive vests and guns to kill as many people as possible.
The pair headed to Turkey in May 2014, and from there traveled separately to Germany via Greece.
In January, they allegedly persuaded Mahood B. to participate in the attack, while Saleh A. established contact with Abd Arahman A. K.
ISIS leadership sent the latter to Germany in October 2014 to take part in the attack, commissioning him to make explosive vests, the statement said.
The plot did not proceed further due to Saleh A.'s arrest, the statement said.
It said the arrests are not related to the UEFA Euro 2016 soccer championship beginning next week in France.
The U.S. State Department issued a travel warning this week over concerns about big events in Europe this summer, particularly the soccer tournament.
Germany has welcomed more people in response to the migrant crisis than any other European nation.
But the public's initially welcoming reception to the new arrivals has gradually cooled over a perceived terror risk associated with the migration wave as well as
high-profile incidents of sexual offenses linked to migrants.