On 18 April 2019, Best announced that he would retire from professional rugby after the 2019 Rugby World Cup. "It is with mixed feelings that I announce my retirement from Ulster Rugby as of the end of this season," said Best. "This feels like the right time for me to go out on my terms, a luxury for which I feel very privileged,".
His final test for Ireland was on 19 October 2019, when Ireland lost to New Zealand, 14-46 in the quarter-finals of the 2019 Rugby World Cup, which was also Best's fourth World Cup tournament. Best was replaced by Niall Scannell in the 63rd minute of the test, receiving a deserved standing ovation from the crowd as he departed the field. His achievements across his career earned his subsequent praise from All Blacks Captain, Kieran Read.
Best played his last game professional rugby match with the Barbarians, on 16 November 2019, captaining the team with the Flying Fijians claiming the Killic Cup 33-31.