Played at the Ryan McBride Brandywell Stadium, the Reds scored twice either side of half time to run out deserving winners.
Cliftonville started well and took the lead on 11 minutes when Northern Ireland international Marissa Callaghan rounded Derry goalkeeper Clare Friel to open the scoring.
As the half progressed, Derry grew in confidence and on 30 minutes Paula McGrory went close to levelling but her right footed shot flashed inches wide.
However, just as the home side were getting a foothold, Reds’ teenager Caitlin McGuinness marked her debut with a goal, bravely heading home at the far post.
The game was over as a contest on 50 minutes when Niamh Connolly scored and she added a second just after the hour mark to complete the scoring.
Only a superb save by Friel kept Cliftonville at bay on 81 minutes when it looked certain that Kirsty McGuinness would open her account for the season.
Overall Derry made it an entertaining contest and can take plenty of positives from the game. Boss Kevin McLaughlin was pleased that his side continue to progress “The excitement and buzz in and around our squad on Wednesday night was nothing that I had ever seen before since the start of my tenure as DCFC Women’s manager.
“And despite the result everyone was still really confident about the path that we are on after the performance we put in last night. We are all well aware that we are not the finished article yet, but everything that we have worked on so far during pre-season was proved during the match on Wednesday night. The players are starting to believe in it and we will continue to build upon that.
"It’s no secret that we are massive underdogs going into every single game in this league and for us its has to be about continuing to make progress. And we are! We look solid defensively and teams are finding us much more difficult to break down in open play.
"Our biggest step forward though is that we are now starting to become an offensive threat and we look like scoring goals throughout the 90 minutes.
"We feel we were unfortunate not to come in at half-time level with Cliftonville and it could be argued that we may have come in 2-1 up.
"However, the other side of this coin is that we are now finding ourselves higher up the pitch in attacking positions. Because of this teams are now scoring their goals against us on their counter attack and this is something we have never had to deal with much before. But we obviously welcome this fact as this proves the progress that we are making.
"Our next step is to prioritise our transition to defensive positions after our own attacking play. If we can improve in this area next, it will be another step forward to bridging that gap between us and the five established sides above us."
Meanwhile City’s near neighbours Sion Swifts Ladies suffered an opening night loss at last year’s runners-up Linfield Ladies.
The Blues got off to an impressive start with a comfortable 3-0 victory at home with striker Alison Smyth netting a brace and the unfortunate Sion goalkeeper Denise McElhinney scored an own goal.