The arraignments come nearly one month after a federal grand indicted Kilpatrick, accusing him of orchestrating an "audacious and far-reaching abuse of the public trust," the Detroit Free Press reported.
The charges carry penalties ranging from three to 30 years in prison if he is convicted.
Arraigned alongside Kilpatrick and his father Bernard Kilpatrick were former aide and close friend Derrick Miller, contractor Bobby Ferguson and Victor Mercado, the former director of the Detroit Water and Sewerage Department.
Prosecutors have accused Kilpatrick of orchestrating a multimillion-dollar scheme to rig bids and extort money from contracts funded with taxpayer dollars.
The 89-page indictment returned in December describes a brazen pay-to-play scheme in which the Kilpatricks allegedly took kickbacks and bribes to steer city business to certain contractors.
Prosecutors allege it was Mercado's department through which many of the allegedly "tainted" contracts were approved.
Not-guilty pleas were entered Monday on behalf of the five in front of U.S. Magistrate Judge Mark A. Randon.
At a subsequent hearing an hour later, U.S. District Judge Nancy G. Edmunds said the "unusual and complex" case won't be on a fast track.
The government proposed a trial date in January 2012, while defense attorneys floated a date of summer 2012.
Defense attorney James Thomas says Kilpatrick is in good spirits and plans to fight the case.