Smooth will have a number of high-profile networked shows that are broadcast throughout the country, alongside re-introduced regional breakfast and drivetime shows.
Klass, who already presents a show on sister station Classic FM, will present a Saturday programme on the Smooth network between 10am and 2pm.
Garraway, meanwhile, will present a new mid-morning show on the Smooth network from 10am to 2pm each weekday. Lynn Parsons currently presents the mid-morning slot.
On London, the TV presenter and former British number one tennis player Andrew Castle will present a four-hour breakfast show from 6am to 10am. Castle will also interview celebrities for a Sunday evening show, 'Andrew Castle Meets'.
Anthony Davis, who joined Smooth in January, will continue to broadcast a drivetime show in London, on AM and on digital. The regional FM stations will broadcast their own drivetime shows.
The introduction of local breakfast shows will mean the breakfast host Simon Bates, who joined Smooth from Capital in 2010, will be leaving the station.
Other national shows will feature Paul Phear on weekday afternoons, the Chris Skinner-fronted 'The Smooth Sanctuary' and Tina Hobley, who will retain her Sunday mid-morning show.
Smooth is available on 97-108 FM in the North West, North East, London, Glasgow and the East and West Midlands, on AM, on DAB and on digital TV. All its stations previously broadcast a single national feed.
The changes follow the blocked merger of Global Radio and GMG Radio. Global Radio has agreed to sell stations including Smooth East Midlands, Smooth North West and Smooth North East to Communicorp to allay competition concerns.
Ashley Tabor, the founder and executive president of Global, said: "[Executive director of broadcasting] Richard Park and his team have assembled an all-star cast for Smooth.
"Andrew Castle, Kate Garraway, Tina Hobley and Myleene Klass joining Smooth tell you just how seriously Global takes the launch of Smooth, and the focus and investment we're putting behind this brand.
"It's a further demonstration of our core strategy of ‘national brands delivered locally’ and it's very important to us. As Smooth becomes one of the country's biggest commercial radio brands, we're investing to make it bigger and better for our listeners and advertisers."