Anana, a 20-year-old bear, had lived alongside 16-year-old Nuka without incident in 2020, having arrived at the zoo last March.
The duo had lived apart from several months, but were reintroduced last week in the hope that they would breed, as part of the 'Zoos & Aquariums (AZA) Polar Bear Species Survival Plan' - which aims to boost numbers of endangered creatures, whose habitats are being increasingly destroyed by climate change.
But Anana sadly died on Monday during an attempt to mate, marking the first time an animal has killed another at the zoo since 1988, according to officials.
The previous instance more than 30 years ago also involved polar bears.
Scott Carter, the Detroit Zoological Society's Chief Life Sciences Officer, said in a statement: "This was completely unexpected and the Detroit Zoo staff is devastated by the loss of Anana in this sudden and tragic event."
Nuka had previously impregnated numerous other female bears 'without showing harmful behavior'.
However, polar bears are known to sometimes turn on each other, with various reports saying some bears have been resorting to cannibalism in the wild due to food shortages caused by melting ice.
Detroit Zoo is also home to one other adult female polar bear called Suka, who - in happier news - recently gave birth to Nuka's two cubs.
While Suka cares for her one of the cubs in a private enclosure, the other is being raised by zoo staff.
A 'cub update' on the zoo's Facebook page last week said: "As you may have heard, twin polar bear cubs were born at the Detroit Zoo to mother Suka on November 17, 2020. Two days later, it was observed that one of the cubs was becoming inactive and appeared to be weak.
"This cub was moved to our Ruth Roby Glancy Animal Health Complex where she was examined by veterinarians and given fluids and formula. She has continued to receive around-the-clock care and bottle feedings (milk mustache featured in photo 2).
"We are thrilled to report that the young cub is thriving! She is steadily putting on weight and has graduated from an incubator to a 'playpen'. Though still behind-the-scenes, this cub will eventually live with other bears in the Arctic Ring of Life habitat."Featured Image Credit: Detroit Zoological Society