The 28-year-old will link-up with fellow Ulster forward Roger Wilson at Franklin's Gardens, while Wallaby lock Justin Harrison will switch from Ravenhill to Bath next season.
Best, renowned for his ferocious tackling, insists he is looking forward to testing himself in the Premiership.
"I've played against English teams and I don't have any problem with people who are bigger than me running at me. I enjoy that!" he said.
"The physical aspect will be different because it is so relentless but I'm looking forward to that.
"The standard of the competition is a step up from the Magners League and this is the perfect time in my career to take it to the next level."
Best has been a regular in the Ulster back row since making his debut in 2002 and won his first cap against New Zealand three years later.
A raft of bone-crunching hits thrust him under the spotlight during victories over South Africa and Australia in 2006, winning the man of the match award against Wallabies.
But he lost his place to Simon Easterby for the ensuing RBS 6 Nations and since spending the World Cup on the bench, has been dropped from Ireland's 22 altogether.
Saints director of rugby Jim Mallinder said: "Neil is a superb addition to our squad.
"He has a strong physical presence on a rugby pitch and the skill to match.
"He also wants to improve as a player and as part of the team here at Northampton.
"All of these are attributes we look for in our players and Neil fits the part."