The 36-year-old Santoro, who is playing his final season on the ATP tour, swapped jerseys with Blake after the match and did a lap around the court to warm applause from the crowd at Bercy indoor arena.
Blake broke Santoro's serve twice in each set, and afterward paid tribute to the Frenchman.
"He's a great competitor, such a classy guy. Someone I've had a lot of tough matches with," said Blake, who next plays fourth-seeded Andy Murray of Britain. "He's had a great career. It's unbelievable how much success he's had in singles and doubles and how well liked he is by his competitors."
Murray beat Mikhail Youzhny in the Valencia Open final on Sunday, winning his sixth title of the season in his first tournament back since injuring his wrist at the U.S. Open in September.
Becker converted all three break chances, and saved two second-set break points and another in the decider. Both players served nine aces.