"It's the worst accident I've seen during my 30 years in this line of work," emergency worker Jonas Hellsten told the local Helsingbord Dagbladet newspaper.
The accident left one person dead, according to police, while 46 people were hospitalized, four of whom had serious injuries and 10 of whom had broken bones. Three firefighters were also among the injured.
Those injured were rushed to hospitals in Helsingborg, Ängelholm and Kristianstad
The crash took place shortly before midday on the Tranarpsbron bridge just northeast of Helsingborg.
Slippery road conditions and poor visibility due to fog are to blame, police told the TT news agency.
"The scene is pretty chaotic," head fire fighter Christer Haraldsson told the TT news agency.
"Several people are stuck in their cars. We have a large number of ambulances on their way and we are sending a bus to evacuate the area."
Emergency crews estimate the wreck involved approximately 100 vehicles, but exact figures remain hard to come by.
A press photographer on the scene said the scene of the accident "stretches as far as the eye can see" and involves cars on both sides of the motorway.
"I can see how an emergency services fuel truck has crashed into a truck, which is now lying across the lanes," Scanpix photographer Björn Lindgren told TT.
"On the other side, I can see two trucks that have rammed into one another, tearing the load from one."
Haraldsson confirmed that an emergency service fuel truck was involved in the crash.
The E4 has been closed in both directions while rescue crews continue their work, and it remains unclear when the road will reopen.
Throughout much of the day, officials were reporting three people had died in the crash, but late on Tuesday night police issued a correction on their website, confirming that one person, had died.
Elsewhere, around ten vehicles were involved in a crash on the E20 motorway northwest of Eskilstuna in central Sweden.
The wreck stopped southbound traffic on the E20, and one person sustained minor injuries.
Snow continued to fall across much of the country on Tuesday, causing a number of accidents on Swedish roadways, with 33 being reported in Stockholm county alone.