Wolfe beat Vienna Williams by a ten round decision to win her first world title, the IFBA Jr. Middleweight title. She beat Gina Nicholas by knockout in three to win the vacant WIBA Light Middleweight title. She then proceeded to beat Shirvelle Williams by knockout in one round on a non title bout.
Next was the vacant IFBA world Super Middleweight title, which she picked up by knocking out Marsha Valley in six rounds. She and Valley fought again, this time with the vacant WIBC's version of the title, and Wolfe won by knockout in round ten.
She avenged her defeat against Mahfood by taking the NABA world Super Middleweight title from her with a ten round decision.
On May 8, 2004, she surpassed Henry Armstrong's record of three world titles at the same time in different weight classes, by gaining the IBA world Light Heavyweight championship, knocking out the defending champion, former NCAA basketball star Vonda Ward, at one minute and eight seconds of round one. Ward was taken to the hospital in serious condition due to damage to her neck and head. She recuperated. Television commentators called it "the greatest knockout in women boxing's history".
Wolfe retained her title in a rematch with Valley, by a sixth round knockout.
A highly anticipated match took place when Ward defended her title on May 8, 2004, in a nationally televised bout with Ann Wolfe, in Biloxi, Mississippi. At one minute and eight seconds of the first round, Ward was the recipient of a right hand to the chin, which left her motionless on the floor for a few minutes. This first round knockout defeat represented not only losing her title, but also her record as being an undefeated fighter. Ward had a neck concussion because she hit the canvas with her neck when she fell. Having been put on a neck protecting collar and given oxygen with a mask, Ward required hospitalization after this bout, and many that saw it on television called for her retirement. It should be noted that Ward's official website DOES NOT acknowledge her severe loss to Ann Wolfe.