MacLean, who joined the Pilgrims for £500,000 from Cardiff on Friday, had to play second fiddle to Rory Fallon, who netted the Argyle equaliser early in a second half dominated by the home side.
Fallon, given a rare first-team start following his move a year earlier, steered home a low cross from man-of-the-match Peter Halmosi to cancel out Bradley Wright-Phillips' first-half opener.
After that, the Pilgrims pummelled Southampton, who nevertheless managed to hang on for a share of the spoils.
Halmosi had a shot brilliantly saved by Southampton goalkeeper Kelvin Davis and MacLean snatched at another chance created by the Hungarian winger as Argyle poured on the pressure.
Southampton had taken advantage of a shaky start by the Pilgrims to go ahead after 12 minutes.
Defender Alexander Ostlund, back in the starting line-up after two months out through injury, played a long ball up from the back which Wright-Phillips - timing his run perfectly - seized upon before chipping the ball past Argyle goalkeeper Luke McCormick.
Once Fallon and MacLean started to win their share of the ball, the Pilgrims were always the side most likely to score.
Davis beat out a shot from Lilian Nalis and then palmed away a low drive by David Norris, a player the Saints along with other Championship sides are said to be interested in.
Saints defender Gregory Vignal made a heroic stop on the goalline after Halmosi had headed the ball towards goal following a brave save by Davis as Fallon latched on to Norris' through-ball.
Saints though could have wrapped up the victory just before Fallon's goal when Wright-Phillips escaped the attentions of Krisztian Timar to send a shot across McCormick and only just wide.