The team announced Tuesday night that Rose was feeling pain in his knee, and an exam and MRI confirmed a medial meniscus tear.
The 2011 NBA MVP played in only 10 games last season before he had surgery for the same injury in November 2013, shelving him for the year, but the Bulls said a timetable for his return will be determined after the operation.
It's unclear when Rose re-injured the knee. He appeared to be rounding into form last month, averaging 22.6 points over his final 14 games before the All-Star break, but he had struggled since returning to the court after the time off.
Rose had eight points on 1-for-13 shooting while playing almost 33 minutes in Monday night's 87-71 victory over Milwaukee. He averaged 10.7 points on 23.5 percent shooting in Chicago's first three games after the break.
It's quite a blow for the surging Bulls, who have won six of seven and appeared to be picking up steam after a tough stretch.
Rose has been dogged by injuries since he won the MVP award. He was limited to 39 games during the 2011-12 season, and tore the anterior cruciate ligament in his left knee in Game 1 of the 2012 playoffs against Philadelphia. He missed the next season altogether, and then last season was cut short by the right knee surgery.
Rose, 26, is averaging 18.4 points and 5.0 assists in 46 games this season.
Cleveland Cavaliers veteran forward Shawn Marion is expected to miss two weeks because of a hip injury.
Marion, who began the season in Cleveland's starting lineup, underwent an MRI exam Monday and the test revealed a strained left hip.