Andy Murray was one of the first stars to take the court on Sunday, against Germany's unseeded Florian Mayer.
The defending champion and World No.3 was made to work hard in the first set but won the second and third sets easily against Mayer. Murray won 7-6 6-2 6-2 to enter the last-16.
Women's star Serena Williams took on 20-year-old upcoming sensation Sloane Stephens as the Arther Ashe stadium was jam-packed for this high octane clash.
The 15-ranked younger player could hardly trouble the World No.1. Serena prevailed 64 6-1 to book a quarters berth.
Czech Republic's Tomas Berdych hardly hard to bat an eyelid as he overcame 31st seed Frenchman Julien Benneteau 6-0 6-3 6-2 to enter the pre-quarters.
Djokovic did not dig deep into his reserves but his overall skills were too much to handle for Portugal's Sousa. Djokovic won 6-0 6-2 6-2.
The World No.1 and top seed will face Spain's Marcel Granollers in the Round 4 clash. If all goes well for Djokovic, he is expected to take on Andy Murray in the semis.