Ex-FBI Director James Comey’s defense lawyer is a longtime ally and former prosecutor known for taking down prominent political players.

Patrick Fitzgerald is advising Comey, who was indicted Thursday on charges related to obstruction of justice. Their ties reach back decades to when both lawyers worked as federal prosecutors in Manhattan.

“He’s gone to one of the best lawyers in the country, who is also his friend, to guide him in this situation,” said Joshua Naftalis, a former Manhattan federal prosecutor. Naftalis, who did not work Comey or Fitzpatrick, is now a partner at litigation boutique at Pallas Partners.

Fitzgerald led prosecutions against Illinois governors Rod Blagojevich and George Ryan. He also steered an investigation that resulted in criminal charges against Scooter Libby, chief of staff to ex-Vice President...