Roddick, who announced Thursday this will be his final tournament, rolled past Tomic 6-3, 6-4, 6-0 and set up a third-round confrontation with Fabio Fognini, who advanced with a 6-4, 6-4, 6-2 decision over Guillermo Garcia-Lopez.
Roddick chose his 30th birthday to announce he was going to retire after the U.S. Open, where he won his only major title.
He said he hoped retirement would not come as soon as Friday, and he had no trouble extending his stay on his sport's biggest stage. Roddick served 13 aces, produced 33 winners to his opponent's 18 and won 5-of-7 break points.
It was the first and last match involving Roddick and the 19-year-old Tomic.
Djokovic, the No. 2 seed, reached the third round by blasting Rogerio Dutra Silva 6-2, 6-1, 6-2. Next up will be 31st seeded Julien Benneteau, who survived against Dennis Novikov 3-6, 6-4, 7-6 (7-1), 7-5.
Isner lost his temper during a confrontation with the chair umpire but finally settled down to defeat Jarkko Nieminen 6-3, 6-7 (5-7), 6-4, 6-3. Isner was upset about a series of late calls while earning a spot in the third round for the fourth year in a row.
Del Potro, who won the bronze medal at the Olympics this summer with a victory over Djokovic, advanced by defeating Ryan Harrison 6-2, 6-3, 2-6, 6-2. Leonardo Mayer will face del Potro in the third round after his 6-1, 6-4, 4-6, 7-5 victory over Tommy Robredo.