The left-back - a former Saints player - has been on trial at Home Park and was snapped up by Pilgrims boss Reid on Thursday after proving his fitness.
Molyneux, 21, could go straight into the squad with Onismor Bhasera pressed into action further up-field in a wide-left berth.
Bhasera has been courting transfer interest from a host of Championship clubs but Reid has rejected any offers for the highly-rated Zimbabwean.
Loan recruit David Button will tussle with Romain Larrieu for the number one jersey after the keeper sealed a loan switch from Tottenham.
Defender Yannick Bolasie is a doubt after damaging his ankle during pre-season.
The League One opener at St Mary's kicks off at 12.15pm.