The bulldozing Polynesian forwards are set to start a Test together for the first time when Australia visit Twickenham in Saturday's opening QBE International.
Mako is inked in at loosehead prop while Billy is favourite to start at number eight, with the pair acting as England's main ball-carriers in the Cook Cup clash.
Billy joined his elder brother at Saracens during the summer and Farrell knows from first-hand experience the damage his club colleagues can inflict.
"They're both big lads - they're massive! I don't like tackling them in training," Farrell said.
"But it's not just that, they have good rugby brains as well. They know exactly what they're doing.
"Mako is the best rugby-playing prop I've ever seen and Billy is a big, big unit who has really good skills and feet. I don't see how you really stop it.
"I don't see how they can't go forward given the way they play. That's not just because of the size of them, but the knowledge and feel for the game that they have.
"What they do is go forward and everyone thinks that is just because they're so big and strong, but it's because of their knowledge and feel for the game."
Farrell was also a team-mate of Mako during the recent British and Irish Lions tour to Australia, an experience the England fly-half describes as "special".
As cover for Ireland's Jonathan Sexton, Farrell made only one appearance in the Test series, coming on as a substitute in the Sydney decider, but the tour has left a positive stamp on the 22-year-old.
"I'd like to have been more involved with the Lions, but I don't look at it with anything other than massive amounts of pride," Farrell said.
"I enjoyed everything about the tour - the rugby side and the learning. I enjoyed hopefully getting better as a player.
"They were a brilliant group of lads and it was a pretty special memory.
"You always back yourself, but this season on the back of that tour I feel more confident when I'm walking out.
"Jonny's a fantastic player and I get on with him really well. I spent a lot of time with him. I definitely learned a lot from him."
The experience also opened Farrell's eyes to the amount of work top players put in behind the scenes.
"The key lesson I took from it was in preparation," he said.
"Some good, good players would do a lot on the field and then stay around for hours after and do all sorts of extra practising - that's why they're good players.
"Then you see what players who have been at the top of their game for a long time do off the field and what they do to the players around them, showing them video and things like that.
"They make sure other people know their jobs so that they can do their jobs too.
"I do work hard, but it opened my eyes a bit as to how they drag other people along, watching sessions and making sure everyone knows their job."