The German club prevailed 66-63 on Wednesday night with Czech Republic international Petra Manakova scoring a game-high 18 points.
Mondeville out-rebounded their hosts 48-28 but turnovers killed them.
The visitors turned the ball over 28 times compared to 16 for the hosts.
Aurélie Bonnan dominated down low for the French side and ended up 12 points and 15 boards.
She and fellow center Valeriya Berezhynska each swatted two shots.
Mondeville blew a golden opportunity to claim an advantage in the opening leg.
They seized a 50-41 lead with 2:13 to go in the third quarter after a Fanny Cavallo lay-up.
Manakova and Yvonne van Daalen buried three-balls to help reduce the deficit to 51-50 by the end of the frame.
A Bonnan lay-up took the Mondeville advantage to 57-54 only for Manakova to hit with two consecutive baskets for a one-point Saarlouis lead.
A Romy Bär basket snapped the final tie with a shot in the lane to make it 51-49 and Candyce Bingham followed with a three-point play for the home side.
An Esther Moisan Niamke shot from the arc for Mondeville reduced the arrears to 64-63 before two Stina Barnert free-throws for the Royals accounted for the final score.
Temeka Johnson finished with 15 points, six rebounds, three assists and a game-high six steals for Mondeville.
The second leg will be played next week in France.