Jeffrey James "Jeff" Weise was born on August 8, 1988, in Minneapolis, Minnesota. His early life was filled with challenges. His parents, Joanne Weise and Daryl Lussier Jr., were a young unmarried couple who separated before he was born. Joanne was only 17 years old at the time of his birth. Under family pressure, she decided to give custody of Jeff to his father, who lived on the Red Lake reservation. Jeff did not live with his mother again until he was two years old, when she reclaimed him and took him to Minneapolis. Later, he described his mother as an alcoholic who sometimes abused him, both physically and emotionally.

In 1992, Joanne started dating a man who was allegedly abusive toward Jeff. The couple had two more children and married in 1998. Throughout his childhood, Jeff moved frequently due to his mother's lifestyle and attended many different schools. By 2002, he had to repeat the eighth grade because of poor grades and absences. He then enrolled in a special education program called the Learning Center.

Jeff faced bullying and teasing starting in middle school. In 1997, when he was eight, he experienced the death of his father, who died by suicide after an event with the Red Lake tribal police. His grandfather, Daryl Lussier Sr., was a police sergeant involved in that standoff. Two years later, Jeff's mother was in a serious car accident due to alcohol use, resulting in severe brain damage. She had to go to a nursing home for rehabilitation.

After Jeff's mother could not care for him, he lived with his paternal grandmother. He left Minneapolis, where he had lived most of his life, to be with her on the Red Lake reservation. Jeff became close with his grandfather and grandmother, who provided him with support. In 2000, his mother and her husband separated, officially divorcing in 2004. By 2003, his mother had moved to an assisted-living facility. She had recovered enough to work part-time and regained her speech, but Jeff chose to stay with his grandmother.

In September 2003, Jeff enrolled at Red Lake Senior High School. He was known to be quiet and withdrawn, and teachers described him as a good listener. Some mentioned his troublesome behavior, while others noted his intelligence but lack of effort in school. Before the events that would later define him, he spent time on the internet, creating dark animations and engaging in online forums that reflected his troubled state of mind. Despite being perceived as a loner, some students felt comfortable talking to him about personal issues.

At approximately 2:35 p.m. on March 21, 2005, Jeffrey James Weise began his shooting spree at his home on the Red Lake Indian Reservation in Minnesota. He retrieved a Ruger MK II .22 caliber pistol from his bedroom and shot his grandfather, Daryl Lussier Sr., twice in the head and ten times in the chest while he was sleeping. After this, he shot his grandfather's girlfriend, Michelle Sigana, twice in the head as she was carrying laundry up the stairs.

Weise then took his grandfather's police weapons, including a .40 caliber Glock 22 pistol and a 12-gauge Remington 870 shotgun, along with a bulletproof vest and drove his grandfather's squad car to Red Lake Senior High School. At around 2:45 p.m., he rammed the squad car into the school building.

As he entered through the main entrance, he encountered two unarmed security guards. He shot and killed one of them, Derrick Brun, with the shotgun, while the other guard, Leann Grant, managed to escape and warned students and staff to take cover. Weise continued through the hallways and shot English teacher Neva Rogers. She attempted to warn other teachers and students but was ultimately shot in front of those who were hiding.

Inside one classroom, Weise asked students if they believed in God. Those who hesitated or said yes were shot. He left the classroom after shooting several students and continued to search for more victims. As the police arrived, Weise shot at two more students before engaging in a shootout with the officers.

During the encounter with law enforcement, Weise was wounded. He retreated back to the classroom where he had already caused harm, killed two more students who were hiding, and ultimately took his own life with the shotgun.

The entire ordeal lasted approximately nine minutes, during which Weise fired a total of 59 shots: 14 at his home and 45 at the school. In total, ten people lost their lives, including Weise.