Blake will move to a career-high fifth in the ATP rankings after beating the Belgian.
Former world number one Roddick reached his first final in 2006 with a 7-5, 6-3 victory against compatriot Robby Ginepri.
Roddick will be hoping to win his first trophy since Lyon last October. He holds a 6-1 record over Blake, his poker-playing partner.
But Blake will take confidence from a semi-final win last month at Queen's Club, London, into the Sunday encounter.
"It helps to know that I've beaten him in the past when it comes to a tight situation." Blake told reporters.
"I'm most concerned about his serve, he hasn't been broken yet this week. If I get my chances, I want to be sure and take them."
Blake weathered the storm against Malisse as the Belgian levelled at a set apiece before the American regained control in the third set.
Roddick needed just 66 minutes to claim his sixth win in seven ATP meetings against Ginepri, who he first played aged 12.
Twice former champion Roddick dominated on serve, with Ginepri praising the effort as the best he has ever faced from his friend.
Roddick never faced a break point, fired eight aces and notched 21 winners against defending champion Ginepri.
"I played tight tennis with not a lot of sloppy errors," Roddick told reporters. "I tried to mix up my serve and give him things he wasn't expecting.
"This was the best tennis I've played all year. I played this match on my terms, I'm happy with the way things are going."
Roddick is aiming to become the first three-time Indianapolis champion since Pete Sampras. Blake will be playing his fifth final of the season, with titles earned in Sydney and Las Vegas.
