The crash, on Lichfield Road, brought traffic to a standstill around Lichfield Road and Riverway.
The collision, which involved a white Land Rover Discovery, a black Renault Scenic, a grey Mercedes E200, a red Ford Focus and a grey Volkswagen, happened around 3pm.
Ambulance and police crews were called to the scene, with two ambulances and a paramedic officer attending.
A spokeswoman for West Midlands Ambulance Service said: "We were called by police at 3:03pm to an RTC involving five vehicles on Lichfield Road, Stafford.
"We currently have two ambulances and a paramedic officer at the scene."
A spokeswoman for Staffordshire Police said: "We were called to reports of an road traffic collision at 3pm this afternoon.
"The collision involved a white Land Rover Discovery, a black Renault Scenic, a grey Mercedes E200, a red Ford Focus and a grey Volkswagen.
"The road was closed between Lichfield Road and Riverway.
"Anyone with any information should message Staffordshire Police on Facebook or Twitter quoting incident number 426 of 20 April, call 101 or alternatively contact Crimestoppers anonymously on 0800 555 111."