Kirby took centre stage during the first leg in Portugal by capping a fine performance with two goals, the first coming after only 80 seconds as she became the club’s record goalscorer.
Millie Bright’s header doubled the lead before Kirby was on target again and a strike from Pernille Harder sent the Blues into half-time with a commanding advantage.
Beth England completed the scoring early in the second half before a demoralised Benfica were reduced to 10 players when Christy Ucheibe was sent off.
Chelsea goalkeeper Ann-Katrin Berger had very little to do but took a ball in the face in the dying seconds to deny the hosts a late consolation goal.
The return leg is at Kingsmeadow next week and Blues boss Emma Hayes will have the luxury of being able to rest some of her star players.
Additional reporting by PA.