With rain delaying play on the other courts at the All England Club, Williams outlasted Kimiko Date-Krumm 6-7 (6), 6-3, 8-6 in a compelling battle under the sliding roof of Centre Court that featured great shot-making from both players.
Williams relied on her big serve at key moments to overcome a gritty challenge from the 40-year-old Japanese player, who was the second oldest woman to reach the second round here in the Open era after Martina Navratilova.
"She doesn't play anywhere near her age," said Williams, who again wore her original one-piece jumpsuit with a triangle cut out in the back, a gold belt and gold zipper.
Following Williams on Centre Court was defending men's champion Rafael Nadal, who cruised past Ryan Sweeting 6-3, 6-2, 6-4 to move into the third round, showing just how tough he'll be to stop as he chases a third Wimbledon crown.
The top-ranked Spaniard, who beat the American for the third time this year, all in straight sets, had only seven unforced errors to go with his 38 winners. Nadal broke Sweeting five times and lost serve just once.
"I was playing very well," said Nadal, who finished in style on the last two points with a running backhand passing shot down the line and a forehand volley into the open court. "The second and beginning of the third I had the match completely under control, but he had a few good shots."
Also advancing was fourth-seeded Andy Murray, who beat Tobias Kamke of Germany 6-3, 6-3, 7-5. The 24-year-old British player never lost serve, saving the only break point he faced, as he again pursues his bid to become the first homegrown male champion here since Fred Perry in 1936.
Three-time Wimbledon runner-up Andy Roddick played the final match on Centre Court, beating Victor Hanescu 6-4, 6-3, 6-4. The eighth-seeded American had 15 aces and only six unforced errors and faced only one break point.
"I felt pretty good out there," Roddick said. "Served well, returned well. There was only a couple shots that I wish I had back there tonight."
The opening contest ended with Date-Krumm hitting a backhand passing shot just wide to lose serve on match point after 2 hours, 56 minutes of play. Among those giving the players a standing ovation were all guests in the Royal Box, including Camilla, the Duchess of Cornwall and wife of Prince Charles.
Williams, who fell behind 5-1 in the first set before climbing back into the match, finished with 12 aces and 45 winners, one less than Date-Krumm. Williams had 24 unforced errors, while Date-Krumm had 31.
"It was tough. She came out and I just couldn't seem to get a game," Williams said. "She played so well and before I knew it the ball was past me every time in the first set."
It was the first time the two players -- who have a combined age of 71 -- have met in their long careers.
"I thought she played unbelievable today," Williams said. "I thought she had some luck on her side, too, with net cords, balls hitting lines. I just thought today was a perfect storm for her to try to get a win. Thankfully, I had some answers."
Williams, who turned 31 last week and is playing in her 15th straight Wimbledon, was pushed to the limit. Date-Krumm kept her off balance by ripping back her serves, hitting flat groundstrokes from corner to corner and sneaking into the net for drop volleys.
The 57th-ranked Date-Krumm made her Wimbledon debut in 1989, reached the semifinals in 1996 and retired later that year until her return in 2008.
"I played my tennis and (showed) I can fight with Venus also," Date-Krumm said. "She's a five-time champion here. She's a great player. So I can fight with her. It was a very, very good match for me."
With rain pounding on the translucent roof, Williams and Date-Krumm put on a fighting display of competitive tennis. The first set lasted 65 minutes, the third went 69 minutes. By comparison, Venus won her first match against Akgul Amanmuradova on Monday in 59 minutes.
It was the third match played under the roof this week, with the tournament schedule already disrupted by rain. The roof was installed before the 2009 tournament and had been rarely used until this week. Matches eventually began after 3 p.m. on the outside courts Wednesday after the showers let up.
The roof remained over Centre Court for Nadal's match, then was opened for Roddick's match against Hanescu.
"The Wimbledon Centre Court with the roof or without the roof, is probably the best court of the world," Nadal said. Nadal's next opponent will be Gilles Muller, who advanced after big-serving Canadian Milos Raonic retired while leading 3-2 in the first set Wednesday. The 31st-seeded Raonic, who led the men's tour with 504 aces in 36 matches coming into Wimbledon, had been considered a threat on grass.
Raonic said he would get an MRI scan on his hip.
"It's around both the inside and outside of the hip," the Canadian said. "A minor pull on the inside, but on the outside, it's regarding the joint. I knew right away. I didn't think I could even lift my leg. It was a pretty sharp pain."
Among men advancing Wednesday were 2010 runner-up and sixth-seeded Tomas Berdych, who downed Julien Benneteau 6-1, 6-4, 6-2; No. 10 Mardy Fish, a 7-6 (6), 6-4, 6-4 winner over Denis Istomin; and No. 17 Richard Gasquet, who defeated Igor Kunitsyn 6-1, 6-4, 6-4.