Ten fire crews tackled the blaze at a 200,000 sq ft (18,580 sq m) warehouse belonging to delivery company Arrow XL on the Blackpole East Industrial Estate since 08:35 BST.
Normally there would be 150 to 200 staff on site at any one time, the firm said.
All colleagues had been accounted for and were safe and well, it added.
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It said its "disaster recovery plan" was in place and the building had been evacuated.
In a statement, the company said plans were "being finalised for our customers to move operations from Worcester to a group owned site".
The Worcester hub, which has been operating since 1994, handles deliveries for Midlands and South West and is one of four hubs and 17 satellite bases.
Earlier Supt Kevin Purcell, from West Mercia Police said it was at the scene of a "significant fire" where it was helping Hereford and Worcester fire service with road closures.
He said: "The fire has been declared a major incident.
Residents were also advised to keep doors and windows closed.
An eyewitness who works for Arrow XL said: "It's a devastating day for all for us.
"I was just driving in so I couldn't get in so it's a bit upsetting and obviously we hope everyone's safe which we think they are."
Crews from Worcester, Kidderminster, Bromsgrove, Malvern, Pershore, Droitwich, Evesham and Ledbury fought the fire.
A fire at a warehouse at an industrial estate in Worcester was declared a "major incident."