Minneapolis police Chief Janee Harteau has resigned at the request of the mayor, who said she lost confidence in her after an unarmed Australian woman was shot dead by a police officer.
Ms Harteau said: "I've decided I am willing to step aside to let a fresh set of leadership eyes see what more can be done for the MPD (Minneapolis Police Department) to be the very best it can be."
Mayor Betsy Hodges said she asked for the chief's resignation.
"I've lost confidence in the Chief's ability to lead us further ... it is clear that she has lost the confidence of the people of Minneapolis as well," she said.
"For us to continue to transform policing - and community trust in policing - we need new leadership at MPD."
Ms Harteau, who worked her way up from the bottom of the department to become the city's first female, first openly gay and first Native American police chief, said she was proud of the work she accomplished and honoured to serve as chief.
But she said the shooting of 40-year-old Justine Damond by one of her officers and other incidents "have caused me to engage in deep reflection".
The chief, who once successfully filed a discrimination and sexual harassment complaint against the police force along with her partner, said she must "put the communities we serve first" despite the department's accomplishments under her leadership.
Ms Harteau was out of the city on personal time for nearly a week following last Saturday's shooting of Ms Damond, a life coach and bride-to-be who was killed by an officer responding to her 911 call of a possible rape.
The state is investigating the shooting. In Ms Harteau's first remarks on the case on Thursday - when she returned to work - she was sharply critical of Officer Mohamed Noor, who is Somali-American, while defending his training.
"The actions in question go against who we are in the department, how we train and the expectations we have for our officers," she said.
"These were the actions and judgment of one individual."
Shortly after the resignation announcement, Ms Hodges nominated Assistant Chief Medaria Arradondo to be the next chief.
Nicknamed "Rondo," he served as the department's public face after Ms Damond's shooting while Ms Harteau was out of town.
Mr Arradondo, who is African-American, has been with the department since 1989.
Ms Harteau has spent her career with the department, starting as a beat cop in 1987 when she was just 22. After working her way up the ranks, she was appointed chief in 2012.
She and her patrol partner, Holly Keegel, were featured in a 1990 episode of the reality TV series Cops.
The partners endured years of harassment from some male colleagues, and it escalated to the point where they felt endangered because they were not getting help when they would call for backup.
The Minnesota Department of Human Rights upheld their discrimination and sexual harassment complaint, which led to changes in training and to discipline against some officers.
Ms Harteau and Ms Keegel got married in 2013 after gay marriage became legal in Minnesota. Ms Harteau told the Star Tribune a year later that they had separated amid the strains of her being chief.