In holding a 13-point lead over rival Fernando Alonso going into the final race of the campaign in Brazil on Sunday, Vettel can finish as low as fourth and still win the title, regardless of the 31-year-old Spaniard's performance.
Vettel has only once slipped below fourth in the last nine races, and that was due to an alternator failure in Italy, so it is no wonder he is a 1-6 favourite with a number of bookmakers.
But on a circuit such as Interlagos, and with rain forecast for the race, Horner knows there can be no conservative tactics to cover Alonso and Ferrari.
"We have to approach this race as we have the previous 19," said Horner.
"We have to go there, attack the weekend, and get the best out of ourselves, the car, the strategy, the drivers and reliability.
"Anything can happen, as we have seen this season. But it is good to be going there with a lead, and we go there determined to close the job off because we're only halfway there."
That is reference to the fact Red Bull departed the United States four days ago with a third consecutive constructors' championship to their name, but with Vettel falling just short.
Horner has always suspected the championship battle would go to the last race, and as he remarked he has "unfortunately been proved right".
But given Vettel has not been off the front row of the grid, nor been out of the top two come the end of the last two races at Interlagos, it would appear Ferrari and Alonso's best hope is for misfortune to befall the German.
Team principal Stefano Domenicali would prefer to focus on what his team can achieve rather than keeping his fingers crossed Vettel does not finish the race.
However, he appreciates the Red Bull can be unreliable on occasion, as was the case with Mark Webber in Austin when he retired with an alternator issue, the team's third this year.
"Pragmatically speaking we know the result has to be better," added Domenicali.
"We have to be in front of Sebastian and we need some drivers in the middle, without thinking of the worst-case scenario.
"This is the approach we need. We know it's not easy because he is driving very well and he has a very quick car.
"But that doesn't change what we have to do. We have to focus on our job and see what will be the outcome of the race.
"But we saw Mark had a reliability issue and that can happen every time.
"However, I want to stay concentrated on the job we have to do, and prepare the car in the best way we can."
Brazilian Grand Prix Air Times (SGT/HKT)
Practice 1: Fri 20:00
Practice 2: Fri (Saturday) 00:00
Practice 3: Sat 21:00
Qualifying: Saturday (Sunday) 00:00
Race: Sunday (Monday) 00:00