Footage of the accident's aftermath carried by local broadcasters showed the twisted wreckages of cars and motorbikes alongside damaged minibuses and trucks.
Regional police commander Tom Odera said the death toll stood at 48 on Friday evening.
"I saw a speeding oncoming trailer. I swerved and escaped hitting him head-on. The person who was behind me thought I wanted to buy something. He overtook me and that is when he was hit. The trailer went off the road and hit other vehicles," said Peter Otieno, a driver.
"I saw about 20 bodies with my own eyes. There were other bodies that were under the vehicle.
The Kenya Red Cross said the lorry rammed more than six vehicles and ran over pedestrians. More than 20 casualties were taken to local hospitals, the Red Cross said.
"The country mourns with the families who have lost loved ones in a horrific road accident in Londiani," Kenyan President William Ruto wrote in a tweet.
"It is distressing that some of the fatalities are young people with a promising future and business people who were on their daily chores."
The accident is one of the most deadly on Kenya's roads in recent years. Last year 34 people died in central Kenya when their bus veered off a bridge and plunged into a river valley
(Reporting by Humphrey Malalo; Additional reporting by Duncan Miriri in Nairobi; Writing by Hereward Holland; Editing by Leslie Adler, Sandra Maler and Alistair Bell)
