The 29-year-old turned a four-stroke deficit into a stunning four-shot victory on home soil at the Madeira Islands Open.
"It is very emotional and I haven't got the words to describe how I feel," world number 306 Santos told the European Tour website after grabbing five birdies in the last seven holes.
"To win my first European Tour event in my own country is very special.
"It was a sensational round, definitely the best of my career. It was amazing to have the crowds here supporting me and it would be difficult to imagine a better win than this.
"I didn't have many bad moments in the round, but the supporters were always there to pick me up and keep me going.
"This is a huge moment in my career."
Swede Magnus Carlsson was second and Dane Andreas Harto third as Spaniard Carlos Del Moral, three clear at the start of the day, fell away to joint fourth with a 73.
Daniel Silva was Portugal's last champion on the circuit at the 1992 Jersey Open.
Jose-Filipe Lima, winner of the 2004 St Omer Open, is now Portuguese, but played under the French flag when he took that title.
Del Moral threw the race for the title wide open by following a bogey on the short eighth with a triple bogey at the 385-yard next.
Harto looked set to be the one to take advantage, taking over top spot after a brilliant front nine 30. But he then had three bogeys in four holes from the 12th.
Santos, a graduate from last season's Challenge Tour whose previous best finish on the circuit was 10th, sank a monster putt on the 17th to all but guarantee victory and then put the icing on the came with another birdie at the last.
Harto said: "The front nine was incredible - I holed some really, really long putts. Unfortunately I just couldn't keep it going and missed some short ones.
"There was a point where I saw a leaderboard and saw I was in front. It's hard not to think about winning.
"I tried to put it out of my head and just concentrate on playing the next shot.
"But this is a great week for me - there are many positives to take from this."
It is the second week running someone has won from four back after 54 holes. Francesco Molinari did it at the Spanish Open.