Karlovic dominated the match from the very beginning till the end thanks to his serve and outclassed Hewitt in both of the sets, winning 6-3 6-2 in just 1 hour and 5 minutes.
The Australian, who won this tournament 4 times in the past, was broken three times throughout the match and found it hard to find any answers when Karlovic serving.
South African Kevin Anderson ousted last year’s finalist James Ward, beating him 4-6 6-3 6-4.
Ward got off to a better start, taking Anderson’s serve in the 9th game of the first set just before serving it out.
However, the South African found his rhythm, and took control of the match to set up a second round encounter against the Ukrainian Sergiy Stakhovsky, who defeated Italy’s Flavio Cipolla 6-4 6-1.
In the other first round matches, Marcos Baghdatis overcame Frederico Gil in three sets 7-6 (2) 4-6 6-2, American lucky loser Ryan Sweeting eliminated Dmitry Tursunov of Russia 6-4 7-6 (6) and Bulgarian Grigor Dimitrov beat American qualifier Bobby Reynolds 6-3 7-5.