The money has been made available through Humber LEP's £30m Growing The Humber Regional Growth Fund (RGF) programme, designed to unlock projects that have the potential to create jobs.
The 12 grants, which have been awarded to businesses either side of the Humber, will help deliver projects costing more than £10m.
Dozens more projects will be going into contract over the next few months.
Lord Haskins, chairman of the Humber LEP, said: "It is pleasing to see the 12 Growing The Humber projects under way, with dozens more in the pipeline, and we look forward to following the progress of these business growth projects.
"The progress of the scheme has been good because of the excellent partnership work in the region, not just with our accountable body partners North East Lincolnshire Council but all of the investment teams at our four local authorities, which has seen projects from across the region being successful in bidding."
Jobs will be created in a variety of sectors, including manufacturing and industrial services, with diverse job roles ranging from production engineers to welders and administration.
One of the companies to benefit from the grant is KwikTuf in Wincolmlee, Hull, which manufactures toughened glass.
It is using its £300,000 grant as part of a £1.5m investment to buy and renovate a 23,000sq ft building close to its existing factory, and to buy a state-of-the-art toughening plant.
The grant will also help the company grow beyond the current factory, which in turn will create at least 11 jobs, with the possibility of up to 15 jobs over the next three years.
Nigel Thomas, managing director of KwikTuf, said: "The additional investment enables our business to start the project earlier than anticipated, which has been vital in terms of retaining customers.
"Changes in legislation over the years have meant that the demand for safety glass is increasing year on year."
"By understanding these market trends and investing wisely in the right equipment, we have reaped the benefits of this increasing demand."
"This principle is the basis for KwikTuf's decision to invest further to position ourselves for future growth in turnover and staff".
"We're delighted with the progress the company has made so far."
As well as providing jobs and demonstrating a confidence to invest in the Humber, Growing The Humber also includes provisions to bring empty buildings back into use.