The Australian last won a race at Silverstone in July 2012, but Horner believes he could yet end team-mate Sebastian Vettel's run of eight consecutive victories at Interlagos on Sunday even though the German is in top form.
"Mark has always been very quick around here," when asked by AUTOSPORT if he felt Webber could beat Vettel in a straight fight.
"Statistically, you'd have to say that with the form Sebastian is in at the moment it's going to be very difficult for him, but never say never.
"The weather forecast looks pretty iffy for the whole weekend so it looks like there is going to be another element.
"This is a track that Mark has excelled at, he has two previous victories here and he has always gone very well here."
Webber's chance to eclipse Vettel
Horner believes that while Webber is highly-motivated to bow out of F1 on a high and hailed his recent form.
Webber has claimed pole position for two of the last four races and would have made it three at Austin had he not underachieved in the final sector of the lap.
"He hasn't struggled for motivation, certainly looking from within the team," said Horner.
"What was important for Mark was that when he called time on his career in F1 was that he was still delivering at a top level.
"He will sign off his career here in Brazil absolutely at the top of his own game."
Horner stressed that his two drivers would be free to race head-to-head for victory on Sunday if the situation arose.
"It will be the same as it has been all year," he said.
"The two of them, unless there are unheard of circumstances, are absolutely free to race."