The 19-year-old seeks her third title of the year at the 6 804-yard Club de Golf Mexico layout, having won her first major title at the Women's PGA Championship last June and added her second consecutive Portland Classic crown three weeks later.
The world No 7 suffered her worst finish of the year two weeks ago in Malaysia, sharing 63rd, and skipped last week's event in Japan, only her second missed tournament of the year, to prepare for her Mexico trip.
Also in the 36-player field is 14th-ranked Anna Nordqvist of Sweden, who shared third in Malaysia. She shared second at the Ochoa Invitational in 2011.
This is the last qualifying event for the Tour Championship next week at Naples, Florida. While 72 players will qualify for the tournament, only the top three in the Race to the Globe can claim the season points crown outright with a victory and only the top nine in the race will have a chance for that crown depending on how all players finish.
Henderson is set for the third and final spot on the Race for the Globe, trailing only Thailand's world No 2 Ariya Jutanugarn, the leader on 4 491 points, and New Zealand's world No 1 Lydia Ko with 4 365.
The next four spots are set with players who, like Ariya and Ko, are idle this week. They will go to South Koreans Jang Ha-Na and Kim Sei-Young, Australia's Minjee Lee and China's Feng Shanshan.
Next are South Korea's Chun In-Gee and Japan's Haru Nomura with Nordqvist 10th and needing a top-20 finish to crack the top nine and give herself a chance at the Globe next week.
South Korea's Park In-Bee, last year's Ochoa winner, will not defend her crown due to a left thumb injury.
"For the past couple months after the 2016 Rio Olympics, I have been focusing on recovering," Park said in a statement. "I had to put on a cast for about four weeks. So far, I'm seeing some positive improvements on my rehab and I've started to hit some balls. However, my injury is still not fully recovered. I will focus on getting fully recovered from the injury and put all efforts to be back on the golf course as soon as possible."
