The road victory, in front of 22,000 at BMO Stadium in Los Angeles, also featured the first use of video assistant referee (VAR) in the NWSL.
Eighteen-year-old rookie Alyssa Thompson, selected with the first pick of the NWSL draft, opened the scoring for Angel City in the 11th minute. The forward unleashed a shot from just outside the 18-yard box that brushed off the fingertips of goalkeeper Abby Smith and into the upper right corner of the goal.
In the 15th minute, Angel City fans thought the home side had its second goal when Jun Endo scored from nearly 40 yards out, but a VAR review overturned the goal due to a foul on the play.
Gotham, who finished at the bottom of the league in 2022, leveled the score in the 55th minute when they were awarded a penalty after a second VAR review. Midge Purce sent her shot from the spot into the upper right corner.
Williams, in her Gotham debut, put the visitors up 2-1 in the 64th minute with a one-touch shot off a pass from Purce.