The £675m fund was announced by chancellor Philip Hammond in October's Budget but the bidding process opens today.
It comes after the report of a panel led by Sir John Timpson, which called for a community-driven approach to transforming the high streets into "community hubs".
Communities minister Jake Berry said: "We all know high streets are changing, we can't hide from this reality.
"But we're determined to ensure they continue to sit at the heart of our communities for generations to come.
"To do this we have to support investment in infrastructure, boosting local economies and ensuring people are able to get the most out of their local high streets."
Black Friday brings some good news
Official figures defied warnings of pre-Christmas doom for retailers
One of the main challenges for high streets is online shopping: in 2000, it accounted for less than 1% of retail sales while in August 2018 almost a fifth of all retail sales took place online.
Projects for those using the fund could include supporting regeneration, reconfiguring space, increasing the number of homes for young and old people, more work space and reducing vehicle congestion.
It caps off a terrible year for retailers, with Poundworld and Maplin among those entering administration, Marks & Spencer and Debenhams deciding to close stores and Superdry, Carpetright and Card Factory among those issuing profit warnings.
Nearly 150,000 jobs have been axed from the sector this year and, with shoppers spooked by Brexit uncertainty, there are fears next year may not be much better.
Worried retailers even launched Boxing Day sales early this year, with Debenhams offering up to 50% off some items before its traditional Boxing Day sale and John Lewis starting its clearance online for some products at 5pm on Christmas Eve.
Boxing Day deals at Marks & Spencer were online at midnight on Christmas Day and supermarkets were also in early, with Sainsbury's, for example, reducing electrical items from 23 December.
Figures show footfall was up in the last few days before Christmas, with 27.4% more trips made to non-food stores in the UK on Christmas Eve this year compared to last, according to Ipsos Retail Performance.
Sportswear and outdoor leisure stores saw the largest gain on last year, up 44.1%, followed by department and general variety stores, up 30.4%.
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Tim Denison, director of retail intelligence at Ipsos Retail Performance, said: "The surge in shoppers to stores seen over the final few days before Christmas will give some solace to those in the sector, when they sit down to enjoy their roast turkeys today, after such a torrid year."
But, of course, an increase in the number of shoppers does not necessarily mean an increase in the amount spent - for those figures, we will have to wait for the various stores' financial results at various times next year.