Mewis hasn't played since Jan. 23 when she came off injured during the USWNT's 6-0 win over Colombia.
Sunday's win means City keep the pressure on Chelsea at the top of the table. Both sides have now played 15 games each and City are just two points behind Emma Hayes' side with a possibly decisive game coming on April 25.
City were the stronger side throughout the game with Birmingham's Hannah Hampton pulling off several good saves in the first half to keep her side in it.
There was little she could do on 40 minutes, however, when Mewis rose above the Birmingham defence to head home a cross from Chloe Kelly.
Mewis got her second of the game and fifth of the season on 52 minutes, tapping in after the ball was cleared off the line.
In a bizarre moment 90 seconds later, Hemp appeared to try to put a low cross into the box but instead directed it into Hampton's net and injured herself in the process.
Mewis was denied the chance of a hat trick when she was subbed off for Georgia Stanway on 63 minutes.
City kept up the pressure, however, and some poor play from Hampton on 66 minutes saw Weir nab the ball off her and score.