Police were called at 10.17am on Thursday to reports of an incident on the M62 between junctions 26 and 27.
It was then established that the 63-year-old woman had in fact fallen from the Oxford Road bridge above the motorway.
She sustained significant injuries and was taken to Leeds General Infirmary for treatment but was later pronounced dead.
Det Insp Stef Wiseman, of Kirklees CID, said: “It is believed there were a number of vehicles on the bridge at the time including a white van with blue writing, a ‘smart’ car and a white Mercedes Sprinter-sized panel van and the occupants of these vehicles may have witnessed this lady fall.
“We are trying to establish the exact circumstances of this incident and we are appealing for those people to contact us. We would also like to hear from anyone else who witnessed the incident or the circumstances leading up to it.”
Anyone with any information is asked to contact Huddersfield CID via 101.