Blake won 6-4, 6-3 and German Benjamin Becker defeated Michael Llodra 3-6, 6-2, 6-2 in the only matches of the day.
All of the seeded players, led by No. 1 Roger Federer, received byes to the second round.
The 37-year-old Santoro, a six-time winner on the ATP Tour, has said he will leave the tour at the end of the year.
Blake will go against No. 4 seed Andy Murray of Scotland in the second round. Becker's foe will be Russian Nikolay Davydenko, the No. 6 seed.