Roddick won the tie-breakers 7-4 and 7-5 to set up an all-American affair with John Isner, who beat Czech Tomas Berdych 6-3, 6-7, 6-2 at the $1.4 million hardcourt event.
Fernando Gonzalez knocked out Tommy Haas of Germany 7-5, 6-4 and will face holder Juan Martin Del Potro, who progressed to the last four when Robin Soderling withdrew with an elbow injury.
Roddick weathered 13 Karlovic aces on the way to his fifth win against the Croatian in a match featuring unusually long rallies for two of the hardest-hitters in the game.
Gonzalez needed an hour and 23 minutes to subdue the 10th-seeded Haas, who was bidding to reach his fourth successive semifinal.
Gonzalez, 29, scored the only service break of the opening set in the 11th game before serving it out.
The Chilean then broke the 31-year-old German twice to take a 5-2 second-set lead before securing the win, his third in four hit-outs with Haas.
Sharapova through
In Los Angeles, Maria Sharapova fought her way into the semifinals of the LA Championships with a 6-4, 7-5 win over Polish teenager Urszula Radwanska.
Sharapova will face Flavia Pennetta in the last four after the Italian stunned second seed Vera Zvonareva of Russia 6-4, 6-2. Romania's Sorana Cirstea upset Agnieszka
Radwanska, Urszula's older sister, to set up a semifinal against Samantha Stosur, who beat Zheng Jie of China.
Cirstea upset the elder Radwanska 7-6, 1-6, 7-5 and will now face Australian Stosur, who reached her second consecutive semifinal with a 4-6, 6-3, 6-4 win over China's Zheng.
Cirstea received treatment for a right foot injury during the second set but hopes to be ready for Stosur.
Last week, Stosur upset Wimbledon champion Serena Williams at the Stanford Classic before falling to eventual winner Marion Bartoli.
Sania Mirza overcame local teenager Rebecca Marino 7-6 (2), 6-7 (3), 6-4 to enter the semifinals of the Vancouver Open tennis tournament, adds IANS. Next up for Sania is another Canadian Sharon Fichman, who defeated her compatriot and doubles partner Marie-Eve Pelletier 6-2, 6-1.
The other semifinal will be between Canadian Stephanie Dubois and American Mashona Washington. Second-seed Dubois had no trouble beating world’s top-ranked junior Noppawan Lertcheewakarn of Thailand 6-1, 6-0, while Washington defeated US-based Canadian Heidi El Tabakh 6-4, 6-3.
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