Williams loses golden oldie clash in final Australian Open warm-up
It was the second consecutive tournament in which the 45-year-old Williams had crashed at the first hurdle after last week's Auckland Classic.
She survived 87 minutes in Hobart against German world number 42 Maria, who is 38, before slumping 6-4, 6-3, having gamely saved six of nine break points.
The first meeting between the pair set a new record for the highest combined age for a main draw match since the WTA Tour was founded in 1973.
Maria said her daughters Charlotte, 12, and Cecilia, four, were probably cheering for Williams, one of their favourite players.
"Everybody loves Venus. I love her too," said Maria.
"For me, to play her was such an honour because I never played her before. It was not easy with all the wind but it was amazing."
Maria last year became the oldest WTA Tour singles winner since Serena Williams in 2020 when she won at Queen's Club in London.
She moves on to a last-16 clash with Hungary's Anna Bondar.
American seven-time Grand Slam champion Williams will now head to Melbourne for the Australian Open, where she has been handed a wildcard five years after she last played there.
Williams, who has played only sporadically in recent years, will be the oldest woman ever at the opening Grand Slam of the year, which begins on Sunday.
Two-time Grand Slam winner Barbora Krejcikova also lost in the first round, needing treatment and strapping on her knee before tumbling out 6-4, 1-6, 7-6 (7/4) to American Peyton Stearns.
The Czech former world number two, now ranked 55, ended her season early last year because of a knee injury, but successfully got through three matches in the United Cup last week, picking up two wins.
Krejcikova, who won the French Open in 2021 and Wimbledon in 2024, missed last year's Australian Open with a back injury.
Stearns will meet Olga Danilovic next after the unseeded Serb beat American defending champion McCartney Kessler in three sets.