Federico Dimarco thumped a free-kick into the top corner, but ex-Southampton defender Maya Yoshida equalised.
Lautaro Martinez then delightfully finished off a slick counter-attack for Inter on the stroke of half-time,
before Tommaso Augello smashed in a left-footed volley after the break.
Sampdoria remain winless after three games this season.
Simone Inzaghi’s Inter side dropped points for the first time this campaign following back-to-back victories.
On Saturday, Napoli maintained their 100% record by beating winless Juventus,
who were playing their 2nd game since the departure of forward Cristiano Ronaldo to Manchester United.