Winger George North, number eight Taulupe Faletau and centre Jamie Roberts, who play for English clubs, all meet the 60-cap criteria and flyhalf Dan Biggar should reach the mark before he joins Northampton next year.
But first-choice scrumhalf Rhys Webb, who has played 28 times for his country, is joining French club Toulon next season and will not be eligible for selection under the new rules.
"The new Senior Player Selection Policy will incentivise the majority of Welsh international talent, both potential and existing, to play their domestic rugby at one of the four Welsh regions," the Welsh Rugby Union said in a statement.
No player with fewer than 60 caps will be selected for Wales if they play for a club based outside the country.
Welsh coach Warren Gatland expects the change to provide a lift to domestic rugby but admitted he would rather have a free hand on selection.
"For me as a national coach, if I was being totally selfish then no I wouldn't have a policy," Gatland said.
"But it's not about what's best for me and the national team, it's about what's best for Welsh rugby.
"The best thing for Welsh rugby and for the Union to support the regions is how do we try and keep a number of the best players in Wales for as long as we possibly can."
(Reporting by Hardik Vyas in Bengaluru, editing by Ed Osmond)
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