The scene of the collision was a curved section of single track on the Metrolink Ventura County Line just east of Stoney Point.

The NTSB blamed the Metrolink train's engineer, 46-year-old Robert M. Sanchez, for the collision, concluding that he was distracted by text messages he was sending while on duty.

This mass casualty event brought a massive emergency response by both the city and county of Los Angeles, but the nature and extent of physical trauma taxed the available resources.

Response included California Emergency Mobile Patrol Search and Rescue (CEMP) as a first responding unit requested by Los Angeles Police Department (LAPD).

Metrolink commuter train #111, consisting of a 250,000-pound (110 t) EMD F59PH locomotive (SCAX 855) pulling three Bombardier BiLevel Coaches, departed Union Station in downtown Los Angeles at 3:35 p.m. PDT (22:35 UTC)[2] heading westbound to Moorpark in suburban Ventura County.

[4][6] The collision occurred after the Metrolink passenger train engineer, 46-year-old Robert M. Sanchez, failed to obey a red stop signal that indicated it was not safe to proceed into the single track section.

[12] The collision occurred after the freight train emerged from the 500-foot-long (150 m) tunnel #28, just south of California State Route 118 near the intersection of Heather Lee Lane and Andora Avenue near Chatsworth Hills Academy.

The events on September 12, 2008 leading up to the collision (all times local):[22][23] The Los Angeles Fire Department (LAFD) initially dispatched a "physical rescue" assignment at a residential address near the scene in response to a 9-1-1 emergency call from the home.

As firefighters were putting out the flames of the burning diesel fuel that had spilled out of the freight engine, patrol officers entered the damaged, smoke-filled train cars to rescue/administer first aid to several passengers who were stranded on the upper decks due to their critical injuries.

[26] A review of the emergency response and the on-site and hospital care was initiated by Los Angeles County Supervisor Don Knabe immediately after the event, and was expected to take 90 days to complete.

[28][29] This event is the deadliest railway collision in Metrolink's history, and the worst in the United States since the Big Bayou Canot train disaster in 1993.

LAFD Captain Steve Ruda reported that the high number of critically injured passengers taxed the area's emergency response capabilities, and patients were distributed to all 12 trauma centers in Los Angeles County.

[34] Many victims were residents of suburban Simi Valley and Moorpark on their way home from work in the Los Angeles area.

[20] The conductor and engineer of the freight train were trapped inside the lead locomotive while it was engulfed in flames; the firefighters who rescued the pair found them banging on the thick glass windshield, unable to escape.

However Los Angeles County Supervisor and Metrolink board member Don Knabe said it was premature to blame the engineer, speculating that "there could always be a technical malfunction where ... there was a green light both ways.

[38] Tyrrell stated that she quit because a Metrolink Board statement called her announcement premature[39] and inappropriate; she maintained that it was proper to get out in front of the story before the NTSB took over the investigation.

After her resignation, some good government proponents praised Tyrrell for her candor, including the chief public advocate with California Common Cause.

[40] The Los Angeles Times also published an editorial by columnist Patt Morrison sympathetic to Tyrrell's position, in which she says, "I am unclear of the concept of how the truth can somehow be premature.

In a subsequent press conference at the scene two hours after Tyrrell's comments, an NTSB official cautioned that the cause of the collision was still under investigation.

[42] "We can say with confidence that the signal system was working," the lead NTSB board member stated at a news conference after the tests.

[12] Before releasing the collision scene and allowing restoration of service, the NTSB also conducted a final sight distance test.

An identical Metrolink train and pair of Union Pacific locomotives were brought together at the point of impact and slowly backed away from each other.

[10] The NTSB member in charge of the investigative team said they were also concerned with possible fatigue issues related to the engineer's split shift.

[43] Before the conclusion of the formal investigation, three witnesses came forward to say that they observed the signal to be green as the Metrolink train departed the Chatsworth station just before the collision.

[50] Two University of Southern California academics used the information in the NTSB statement to determine that the last text message sent by the Metrolink train's engineer would have been sent a few seconds after he had passed the last red signal.

[60] The National Transportation Safety Board (NTSB) member leading the investigation also said she was convinced that such a system "would have prevented this accident".

It required Class I Railroad mainlines with regularly scheduled intercity and commuter rail passenger service to fully implement PTC by December 31, 2015.

Regarding the other 171 miles of Metrolink track that are owned by freight lines BNSF and UPRR, the agency states as of 2017 that they are "working towards PTC interoperability".

In dividing the $200 million among the 25 dead and more than 100 injured in the Chatsworth case, Los Angeles Superior Court Judge Peter D. Lichtman, who characterized the awards as "judicial triage", stated victims were undercompensated by at least $64 million, admitting that awards were unlikely to cover future medical expenses.

There are also 25 markers on the grounds to commemorate each victim as well as a seating area and a plaque in remembrance to the 2005 Glendale train crash.