The deputy prime minister said Southend's new "city deal", officially launched later, would provide support for 375 businesses.
The central library will also be developed and the borough council will buy empty sites in the town centre.
Mr Clegg said: "This city deal puts power in the hands of local people."
Southend is among the second batch of towns and cities to sign up to the city deal scheme, which is designed to increase growth.
Certain powers, such as the ability to set and spend budgets, are devolved from central government to local authorities. Mr Clegg said this would provide "a real chance of changing the fortunes of thousands of people across Essex".
The £6m of funding would include £2.5m from government, £3m in private investment and £670,000 from local government, he explained.
He also said the deal would see the redevelopment of Victoria Avenue and deprived wards in the centre of the town.
Greg Clarke, minister for cities, will sign the deal at the Civic Centre.
"Southend has the potential to be a driving force for growth in the South East," he said. "It is a great place for businesses to locate, expand or start up."