Blake beat 2002 Australian Open champion Thomas Johansson 7-5 7-6 while Roddick, playing his first match since his five-set quarter-final loss to Frenchman Richard Gasquet at Wimbledon, passed wildcard Alex Kuznetsov 6-4 6-0.
The second-seeded Blake believes the momentum he came to Indianapolis with following a final showing at Los Angeles last week, when he lost a three-set battle to Czech Radek Stepanek, helped him take out the Swede.
"Luckily I got a lot of confidence coming from the final in LA," Blake said. "I was able to go for my shots when set points down because I was able to have that confidence."
Blake broke Johansson's serve in the 11th game of the first set and then served out the set to love with an ace on the final point.
In the second set tiebreaker, Johansson had two set points, but the world number 10 Blake won 11-9 on his third match point when Johansson netted a backhand.
TOUGH DRAW
"It's definitely a tough draw," Blake said. "I can't say I was excited to see him in the first round. He can get hot and win any tournament so I'm glad to get through it."
Roddick took advantage of four of 11 break point opportunities in the match, breaking serve in the fifth game of the first set.
In contrast, Roddick never offered the 191st-ranked Kuznetsov an opportunity to break his serve.
"I actually don't think I served that well tonight, but I was playing clean tennis," said Roddick, who won the title in 2004 and 2005. "(Clean tennis) means not a lot of unforced errors and I was pretty well putting the ball where I wanted it."
Fourth seed Mardy Fish fought off two match points and patella tendonitis in his right knee to win a 2-6 7-5 7-5 first-round match over fellow Floridian Vince Spadea.
Third-seeded Dmitry Tursunov defeated American journeyman Michael Russell 6-3 7-5, while sixth seed Lee Hyung-taik of South Korea beat Donald Young 6-2 6-4.
Nicolas Kiefer of Germany withdrew from the tournament because of a left knee injury that forced him out of last week's Los Angeles semi-final.