Mohammed snapped up three wickets for 19 runs to unsettle the top order and restrict the homeside to 128 for five in their 20 overs at Manuka Oval.
16 year old Mathews, in her debut year for West Indies, batted throughout the innings to be unbeaten on 62 as the visitors got to 122 for four before the overs ran out.
Allrounder Ellyse Perry who opened the batting was the star of the Australian innings with a top score of 62 retired out.
She teamed up with Delissa Kimmince in a solid opening partnership that produced 58 runs.
Perry, who faced 52 balls, hit ten fours but did not receive adequate batting support as Mohammed ran through the top order shattering the stumps of opener Kimmince for 11, and removing Jess Cameron and Nicola Carey cheaply.
Matthews, who made her T20 International debut for West Indies against New Zealand a month ago, opened the batting with a commanding display but was running out of partners as the visitors slid to 68 for four.
She occupied the crease for 79 minutes facing 52 balls smashing six fours and two sixes in the process but despite her best efforts was unable to lift the run rate before the overs expired.
Captain Merissa Aguilleira was not out on 15.
The defeat was the second for West Indies women who suffered a nine wicket loss to Cricket Australia Women’s X1 in the first game on Tuesday.
West Indies Women and Australia women will play four T20 internationals and four One-Day International matches starting November 2nd.
Summarized Scores:
Cricket Australia Women’s XI: 128/5 (20 Overs). Ellyse Perry 62, Rhiannon Dick 26*, Delissa Kimmince 11, Grace Harris 8*; Anisa Mohammed 4-0-19-3, Deandra Dottin 2-0-10-0, Shamilia Connell 4-0-22-0, Hayley Matthews 3-0-21-0.
West Indies Women: 122/4 (20 Overs). Hayley Matthews 62*, Merissa Aguilleira*+ 15, Kycia A Knight 11, Britney Cooper 9; Angela Reakes 3-0-6-2, Grace Harris 3-0-18-1, Kara Sutherland 3-0-19-1, Megan Schutt 3-0-13-0.
Cricket Australia Women’s XI won by 6 runs