Continuing from where they left off last season, Djurgardens got ahead early enough as Hayley Dowd opened the scoring in the 10th minute before Hanna Ekengren doubled the lead 15 minutes later.
After the restart, Rachel Bloznalis grabbed the third goal of the encounter in the 70th minute to bury comeback hopes for Uppsala before Motlhalo wrapped up the triumph two minutes from time.
South Africa s Motlhalo featured from the start to the finish of the encounter, alongside Ghana s Portia Boakye in Djurgardens.
Having opened her second campaign in Sweden with a goal, the Banyana Banyana star is looking to surpass her personal best last season, where she scored twice in 20 games.