serving at 1-2 0-30, Williams stuck a down the line forehand wide which she followed up with a netted inside out forehand down the line to drop serve and trail 1-3.
Then serving down 1-4, Williams committed three foot faults in a row before serving up a safer slower serve at 15-40.
Marino punished the serve by stricking a down the line backhand return winner to break serve and lead 5-1.
Williams netted three forehands to lose the following game.
The American would finish the middle set after losing the last five games to drop the set in 27 minutes.
Williams struck two consecutive doublefaults but also a 82 miles per hour down the line forehand winner to hold her opening service game of set three and lead 1-0.
Before the match, her first singles action of 2022, there had been a question of if Williams would wear her own clothing line Eleven or dress from the clothing line Lacoste which had recently sponsored Williams.
Williams then appeared on the tennis court wearing a top and skirt with no logo, Lacoste logoed wrist bands and shoes and a Eleven logoed visor.
Following several Marino errors and two back to back Williams aces, the American took final set leads of 3-0 and 4-1.
However Williams' level of play would drop in the second half of set three as she struck several forehand errors and doublefaults.
Williams would finish the match with 13 doublefaults after losing the last five games of the match.
The American will look to shake off the rust from her game at next week's National Bank Open presented by Rogers at Toronto, Canada where she is entered in the singles draw with her sister as well Serena Wiliams.
Being on opposite sides of the draw, the Williams sisters could only possibly face each other in the Toronto final.
Venus Williams is scheduled to play Jill Teichmann of Switzerland in Toronto in her first round match most likely Monday or Tuesday.