Roddick defeated Michael Russell 6-3, 6-4 to set up a match with John Isner.
After struggling to win matches early in the year, Roddick pulled off a surprise victory over Roger Federer in Miami.
Roddick fell in the third round at Wimbledon, but he emerged as champion in a tune-up tournament for that major championship.
Isner waited through a rain delay late Friday before advancing with a 7-6 (9-7), 6-4 victory over Jack Sock.
Roddick holds a 3-2 edge over Isner, but this will be their first meeting in 2012.
The other semifinal will send Go Soeda against Gilles Muller. Soeda was a 6-2, 6-1 winner over Kei Nishikori and Muller defeated Matthew Ebden 6-4, 6-4.
Swim Week Miami Beach 2014 [PHOTOS]