Santos, the 2012 European Tour rookie of the year, had five of his eight birdies on the day on the front nine of the Doha Golf Club for a one-stroke lead over Alexandre Kaleka, Anthony Wall and Peter Whiteford. Five more players are at 5-under 67 and 13 others are just three strokes off the lead.
Defending champion Peter Lawrie is at even-par 72 and tied for 70th place.
Kaleka had seven birdies and one bogey while Wall and Whiteford each were bogey-free Wednesday.
Santos opened play on the second nine with a birdie at the 10th hole. His lone bogey came at the par-4 11th hole but he came back with a birdie at 12. He made the turn at 2-under after a birdie at 16.
He piled up five birdies on the front side, capping the round with birdies at Nos. 8 and 9 in taking the lead. He beat par on both par 3s and both par 5s on the side.