The plans are for a mixed-use development comprising 1,700 houses and around 180,000 sq ft of employment space.
The 189-acre scheme, which will be known as Rivington Chase, also includes retail and leisure units.
Horwich Vision, a joint venture between Bluemantle and Emerson-owned Orbit Developments, has lodged the plans in partnership with Bolton Council.
A joint statement was released from Jim Caldwell, chairman of Bluemantle and Peter Emerson Jones, chairman of Emerson.
It said: “We have been working closely with Bolton Council, and other key stakeholders over a number of years to reach this point and we look forward to seeing the transformation of the site.
“Many of the existing buildings are reaching the end of their useable lives and a number are no longer capable of being occupied.
“The time is now right to commence the mixed use regeneration of this under-utilised site and to open the next chapter in Horwich’s evolution creating contemporary housing and many jobs.”
Apart from four original properties, which are part of the ‘heritage core’ of the site, the remaining buildings will be demolished. The overall scheme will represent a total investment of about £260m and is expected to take 12 to 15 years to complete.
Bolton Council leader Cliff Morris said: “The development of the former Loco Works is a key part of our economic development plans for the borough. It is a development of regional significance.”