"After 10 years of service at Old Trafford, @ChrisSmalling has left #MUFC to join Roma on a permanent deal. Thank you and good luck in Italy, Chris," United tweeted.
Smalling, 30, impressed during his loan spell with the Serie A side last season and has joined Roma on a permanent deal.
The defender said he was "gutted" to end his loan spell at Roma after helping them secure a fifth-place finish. He made 30 league appearances and scored three goals.
Sources had told ESPN that United were willing to offload Smalling this summer in order to raise extra funds for new players.
Roma boss Paulo Fonseca told ESPN in May that the club wanted Smalling to extend his stay due to his performances and professionalism.
Roma sit 10th in Serie A after four points from their first three matches. The started the campaign with a 0-0 draw at Verona, but were handed a 3-0 loss after fielding on an incorrectly registered player.
During his 10-year spell at Old Trafford, Smalling won two Premier League titles, the Europa League, an FA Cup and League Cup.