In action for the first time since the WTA Tour season was suspended in March due to the coronavirus pandemic, Serena edged past Bernarda Pera.
The top seed at the WTA International event, Serena recorded a 4-6 6-4 6-1 victory after being five points from defeat.
The 23-time grand slam champion raced through the final set, losing just seven points on serve to advance in Lexington.
Awaiting Serena in the second round is Venus, who was too good for Victoria Azarenka 6-3 6-2.
The sisters will meet for the 31st time, with Serena holding an 18-12 win-loss record over Venus.
Sloane Stephens had endured a tough start to 2020 before the season was suspended, and the 2017 US Open champion suffered another loss.
The seventh seed was well beaten by qualifier Leylah Fernandez 6-3 6-3 to slip to a 1-6 win-loss record this year.
The only other seed in action was Yulia Putintseva, who brushed past Ajla Tomljanovic 6-0 6-4.
Coco Gauff, 16, was pushed in her opener, overcoming Caroline Dolehide 7-5 7-5.
CiCi Bellis, Shelby Rogers, Jil Teichmann, Anna Blinkova and Olga Govortsova also advanced.
Former US Open champion Stephens, ranked 49th in the world, defeated Dodin 6-7 (6-8) 6-4 6-2.
Stephens progresses to the second round where the top seeds, including top three Ash Barty, Naomi Osaka and Simona Halep, will be introduced and she will face 28th seed Amanda Anisimova.
Danielle Collins, Wang Qiang, Alize Cornet and Caroline Garcia were among the other winners on Wednesday, while Svetlana Kuznetsova bowed out.
SLOANE FIGHTBACK
Stephens had endured a dismal start to 2021, enduring an 0-4 win-loss record to begin the year.
The 28-year-old American was made to do it the hard way against Dodin on Wednesday, dropping the first set in a tie-break.
Stephens improved on her return in the second set, winning 73 per cent of points off Dodin's second serve before running away with the match in the last.
"It's been a rough one for me lately, so I'm really pleased to get through that, fight my way through it and make it happen somehow," Stephens said post-match.
FORMER MAJOR WINNER GONE
Two-time grand slam winner Kuznetsova was the major first-round casualty, going down 2-6 6-2 6-1 to France's Alize Cornet.
Kuznetsova, who is now ranked 35th in the world, bows out with Cornet to face ninth seed Petra Kvitova.
Collins got past France's Kristina Mladenovic 6-3 6-3 with the 40th-ranked American setting up a second-round clash with 32nd seed Veronika Kudermetova.
Wang, ranked 38th in the world, also progressed despite dropping a set in a 6-1 3-6 6-3 win over Spanish qualifier Aliona Bolsova.
SECOND-ROUND MATCH-UPS
The round of 64 will commence on Thursday, with third seed Halep to face Garcia who got past another Romanian, Mihaela Buzarnescu 6-1 6-2.
Top seed Barty will be in action against Slovakia's Kristina Kucova, while fourth seed Sofia Kenin will take on former top-10 player Andrea Petkovic.
Second seed Osaka has an assignment against 77th-ranked Australian Ajla Tomljanovic, while 14th seed Victoria Azarenka is already into the third round with opponent Laura Siegemund withdrawing after her win on Tuesday.
The 2017 US Open champion triumphed in two hours and 29 minutes over the Australian, winning 4-6 6-3 6-2 in Guadalajara.
Stephens, who will play Russian Anna Kalinskaya in the last four, had not reached a hard court semi since the 2018 WTA Finals.
But the American was forced to do it the hard way after losing the first set, saving nine of 13 break points across the match, with her ability to win second serve points proving key.
Colombian fourth seed Camila Osorio was bundled out in 80 minutes by Kalinskaya 6-4 6-1.
There was also a straight-sets win for Marie Bouzkova after she defeated third seed Sara Sorribes Tormo 6-4 6-1.
She will face Wang Qiang in the last eight, who proved too good for Slovakian Anna Karolina Schmiedlova 6-2 6-3.
Stephens – the American fifth seed – ended her drought by outlasting Emma Navarro 6-4 5-7 6-1 in Monterrey on Monday.
Prior to this week, Stephens had featured in four tournaments without a win, including a first-round exit at the Australian Open.
But the 2017 US Open champion finally opened her account for the year via the WTA International event after two hours, 17 minutes.
Former world number one Williams and her winless year continued, however, following a 4-6 6-3 6-2 defeat to qualifier Anna Karolina Schmiedlova.
Seven-time grand slam winner Williams battled but the 39-year-old was eventually eliminated after two hours, 29 minutes on court.
Elsewhere, Wang Yafan, Rebecca Peterson, Olga Govortsova, Astra Sharma and Marie Bouzkova progressed to the second round.
The 29-year-old American triumphed 6-4 6-4 over Watson in one hour and 27 minutes in Austin.
The 2017 US Open champion firmed into favouritism in Austin with third seed Anastasia Potapova knocked out by USA's Katie Volynets in a thrilling three-set encounter.
Volynets came from a set down and also 5-0 down in the third frame, needing two hours and 19 minutes to get past Potapova, winning 5-7 6-2 7-5.
Potapova's exit follows top seed Magda Linette's first-round defeat, while second seed Zhang Shuai withdrew due to illness on Tuesday.
Stephens has seven career WTA titles to her name, the last coming in February last year at the Abierto Zapopan in Mexico.
Varvara Gracheva defeated Anna Blinkova 6-3 6-7 (5-7) 6-1, while American wild card and Texas local Peyton Stearns beat Mirjam Bjorklund 6-3 7-5.
At the Monterrey Open in Mexico, third seed Donna Vekic progressed to the quarter-finals with a 6-3 6-2 victory over Emma Navarro.
Fifth seed Zhu Lin accounted for Rebecca Marino in three sets, while Ysaline Bonaventure also needed three frames to beat Kamilla Rakhimova.
The 2017 US Open champion qualified for her first final since 2018, winning 3-6 7-5 (ret) with Russian opponent Anna Kalinskaya succumbing to injury late in the second set.
Kalinskaya retired shortly after Stephens claimed the second set having battled through back pain for several games, with the match moving close to two hours.
The Russian had shown signs of injury during Friday's quarter-final win over Camila Osorio which she won in straight sets, yet Kalinskaya raced into the lead in the first set against Stephens.
Bouzkova, who knocked out reigning champion Sara Sorribes Tormo in Friday's quarter-finals, triumphed 6-3 6-3 oover Qiang Wang in one hour and 31 minutes.
The 23-year-old Czech is ranked 96th in the world and has never won a WTA Tour singles title.
Stephens won in straight sets but it took almost two hours, triumphing 7-5 6-4 over the Frenchwoman ranked just outside the top 100.
The 28-year-old American was dominant on her first serve, while she broke her opponent five times throughout the match.
Stephens, who is the sixth seed, will play Daria Saville in the last eight after the Australian eased past qualifier Caroline Dolehide 6-1 6-3 in one hour and seven minutes.
Third seed and defending champion Sara Sorribes Tormo made light work of Poland's Magdalena Frech 6-0 6-2 to set up a quarter-final meeting with Marie Bouzkova.
Colombian fourth seed Camila Osorio needed just over two hours to get past Hailey Baptiste 1-6 6-3 6-3, fighting back after a lopsided first set.
Stephens, who is currently ranked 73rd in the world, having been number three on the WTA Tour in 2018, triumphed 6-7 (5-7) 7-5 6-1 over Watson in two hours, 50 minutes on Wednesday.
In a see-sawing match, there were six breaks in the opening set, as Watson got the edge early on Stephens' serve at the WTA Premier 1000 event.
Stephens steadied by claiming a late break in the second to level the match, before dominating the third set.
Playing at her 10th Indian Wells Open, Stephens won seven consecutive games after the match was 5-5 in the second set.
"After the first set, that was disappointing to lose that one, but I felt like it was a battle and I was still in the match," Stephens said. "I knew I had to keep fighting and that's what I did, and I'm just really pleased to have squeaked out a win here."
KEYS ON SONG IN OPENER
Former world number seven Madison Keys moved through to the second round with a 6-0 7-5 win over fast-finishing Estonian veteran Kaia Kanepi.
American Keys won 21 consecutive points as part of a streak where she clinched the first nine games of the match, withstanding Kenapi's late push.
Keys will take on Russian ninth seed Anastasia Pavlyuchenkova for a spot in the third round.
SAMSONOVA, MARTIC, ROGERS AND PUTINTSEVA PROGRESS
Liudmila Samsonova, who made the fourth round at Wimbledon earlier this year, needed more than two hours to get past Ukrainian qualifier Kateryna Kozlova 6-4 7-6 (8-6).
Samsonova will face countrywoman and 25th seed Veronika Kudermetova in the second round.
Petra Martic won through to take on second seed Iga Swiatek with a 6-4 6-4 victory over American wildcard Katie Volynets.
Ash Barty's US Open conqueror Shelby Rogers claimed her 25th win for the year, getting past Ukrainian Anhelina Kalinina 7-6 (7-2) 6-2, while Yulia Putintseva won 7-6 (7-2) 6-1 over experienced German Andrea Petkovic to set up a showdown with fellow Kazakh player and 13th seed Elena Rybakina.
Stephens broke through for her first win of 2020 to book her spot in Wednesday's second-round match following a difficult start to the year.
But the American fifth seed was upstaged by 17-year-old Fernandez, who rallied past the 2017 US Open champion in three sets midweek.
Fernandez was a surprise finalist at last week's Mexican Open in Acapulco, where the Canadian reached her maiden WTA decider.
The in-form teenager moved through to back-to-back quarter-finals after prevailing in more than two hours against Stephens, with either top seed Elina Svitolina or Olga Govortsova awaiting.
Elsewhere at the WTA International event, sixth seed Rebecca Peterson defeated Kateryna Bondarenko 7-6 (7-2) 7-5, seventh seed Wang Yafan outlasted Astra Sharma 7-6 (7-5) 4-6 6-3 and ninth seed Marie Bouzkova beat Anna Karolina Schmiedlova 6-4 6-1.
Stephens went into the Mexico event as top seed but lost to Slovakian world number 151 Kristina Kucova 6-2 6-2.
The 27-year-old American is now 0-4 to start the 2021 WTA Tour season and has won only one set all season.
Stephens, now ranked 48th in the world, only managed to win 32.4 per cent of points on her first serve, with Kucova converting seven of 14 break points in the match.
Second seed Nadia Podoroska was also a first-round casualty on Tuesday, going down 6-4 6-4 to Russian qualifier Anna Kalinskaya.
In the late match, Eugenie Bouchard went down to China's Lin Zhu 7-5 7-6 (6-3).
American sixth seed Stephens triumphed 7-5 1-6 6-2 in an epic final which lasted two hours and 28 minutes against 96th-ranked Bouzkova.
Stephens, who won the 2017 US Open, has struggled to re-discover her previous levels of success in recent years, having gone undefeated in the first six WTA singles finals of her career and reaching the world number three ranking.
But Sunday's triumph – Stephens' seventh career WTA title - marks a major return to form for the 28-year-old who lost in the first round of last month's Australian Open to Emma Raducanu.
Stephens had trailed 4-1 in the first set but hit back before Bouzkova double faulted on break point at 5-5.
However, the Czech responded in a one-sided second set, breaking Stephens early and never looking back.
The American claimed the first break of the deciding set at 3-2, with Bouzkova letting slip a 40-0 lead, with Stephens' forehand leading her to victory.
Svitolina, 28, had been off the tour for a combination of injury and pregnancy, but was back in action for the first time since giving birth to her and male tennis player Gael Monfils' daughter Skai in October.
The Ukrainian, who reached both the Wimbledon and US Open semi-finals in 2019, won the first set after rallying back from 3-1 down in a tie-break
But the Kazakh world number 47 responded and prevailed 6-7 (3-7) 6-2 6-4 in two hours and 48 minutes, with Putintseva sapping her opponent's energy with frequent drop shots.
Former Australian Open champion Sofia Kenin was on track for victory in a topsy-turvy clash with Aliaksandra Sasnovich before rain intervened, forcing it to be re-scheduled for Tuesday with the American leading 6-1 6-7 (5-7) 3-0.
World number 50 Sloane Stephens fought back after an early scare to beat qualifier Louisa Chirico 3-6 6-1 6-2, while Alize Cornet breezed past Fiona Crawley 6-0 6-2.
Jil Teichman was one of three seeds to lose in the first round, going down 6-2 3-6 6-2 to 17-year-old Linda Fruhvirtova.
Ukrainian 11th seed Anhelina Kalinina lost 7-6 (8-6) 6-4 to Anna Kalinskaya, while 10th seed Zhang Shuai was beaten 6-4 1-6 6-3 by Julia Grabher.
Eugenie Bouchard returned for the first time since the 2023 Australian Open due to injury with a win over Ylena In-Albon 6-3 6-2 at the Copa Colsanitas in Bogota.
Third seed Nuria Parrizas Diaz was knocked out by Briton Francesca Jones, who is ranked 817th in the world, 7-6 (7-3) 6-1 in a major shock.
Teichmann produced an astonishing fightback to beat fourth seed Svitolina 2-6 6-4 7-6 (7-5) at the Caja Magica.
Unseeded Swiss Teichmann came from a set and a break down to claim the scalp of the world number five, who squandered a commanding 5-1 lead in the final set.
Svitolina saw six match points come and go in an incredible deciding set, opportunities she was left to rue when the 40-ranked Teichmann won a tie-break to end a contest that took two hours and 33 minutes to settle.
World number one Barty extended her winning run on clay to 12 matches with a 6-2 6-1 success over Shelby Rogers.
Barty claimed her third title of the year in Stuttgart last weekend and the Australian needed just an hour to send Rogers packing, losing just two points on her first serve and not facing a single break point.
French Open champion Iga Swiatek was also an emphatic winner, easing past another American in the form of Alison Riske 6-1 6-1.
Swiatek, making her debut in this tournament, has won 16 consecutive matches on clay after blowing Riske away.
Defending champion Kiki Bertens beat 15-year-old Victoria Jimenez Kasintseva 6-4 6-0, while Petra Kvitova progressed when opponent Marie Bouzkova retired due to hand injury after the Czech won the first set.
Garbine Muguruza was forced to withdraw ahead of her meeting with Sloane Stephens due to a leg injury. Belinda Bencic, Angelique Kerber and Johanna Konta were among the other winners in the Spanish capital.
British player Swan, who will be competing on a wildcard at Wimbledon, scored a 2-6 6-4 6-2 victory over her American opponent.
Although Stephens has not been regularly hitting the heights of her 2017 Flushing Meadows triumph in recent seasons, the world number 48 would have fancied getting past Swan on Sunday.
The 23-year-old Swan needed a wildcard just to get into qualifying for this event in Germany, and she is due to play doubles alongside Stephens on Monday.
The match began well enough for Stephens, but Swan began to relish the matchup and levelled the contest before dominating the deciding set. Swan let three match points slip by, serving two double faults as the tension got to her, but the win was secured when Stephens drilled a forehand into the net.
Speaking in an on-court interview, Swan said: "It feels great. Sloane is an amazing player. She's a grand slam champion, and you can't get much better than that.
"We're actually playing doubles together tomorrow, so hopefully that'll be fun. I'm so happy to come through that one. It's my first tournament on grass not in England, so it's been fun so far, and it's probably my best result."
Other winners on Sunday in Bad Homburg included Caroline Garcia and Kamilla Rakhimova, who upset eighth seed Liudmila Samsonova.
At the Eastbourne International, where Serena Williams is due to make her tennis comeback by playing doubles in the coming days, first-round winners on Sunday included Marta Kostyuk, Kaia Kanepi and Sara Sorribes Tormo.
Poland's Magdalena Frech enjoyed a 6-3 6-0 stroll against Zheng Qinwen, the 19-year-old Chinese player who beat Simona Halep before causing Iga Swiatek plenty of problems at the recent French Open.
The 2022 French Open and US Open champion triumphed 6-4 4-6 6-1 in two hours and two minutes, bouncing back strongly after losing the second set.
Zheng's power and forehand top spin proved challenging for the Pole, who was solid from the baseline to secure her 11st tour quarter-finals appearance this season.
The Chinese had broken Swiatek to lead 1-0 in the third set, but the top seed responded in trademark style, improving her record in the United States this season to 21-1.
Swiatek will take on eighth seed Coco Gauff in the quarter-finals, with the match-up marking a re-match of this year's French Open final.
Gauff worked her way into the last eight with a 6-4 4-6 6-3 victory over 2019 US Open champion Bianca Andreescu.
The 18-year-old American also had to fight back from a set down in the third set to win in a match that lasted just over two-and-a-half hours.
Third seed Aryna Sabalenka fought back from a lopsided opening set to knock out American Sloane Stephens 1-6 6-3 6-2 in two hours and one minute. The Belarussian will take on Donna Vekic in the next round.
Second seed Paula Badosa eased into the last eight, winning in 53 minutes against American qualifier Louisa Chirico 6-0 6-3. Badosa will face Danielle Collins in the quarter-finals.
Madison Keys triumphed over eighth seed Daria Kasatkina 6-4 6-3 in one hour and 27 minutes to secure a quarter-final date with fourth seed Jessica Pegula.
Gracheva, ranked 88th in the world, needed two hours and 31 minutes to get past Linette 6-3 4-6 6-4 in Austin.
The Pole had led 2-0 in the third set before Gracheva hit back with three breaks in the final frame to run away with a shock victory.
Linette's early exit followed that of second seed Zhang Shuai who withdrew from the tournament on Tuesday due to illness.
Fifth seed Sloane Stephens had no such troubles, progressing into the second round with a 6-3 6-3 victory over Taylor Townsend.
Fourth seed Danielle Collins won 6-7 (7-9) 6-2 6-4 over Magdalena Frech in two hours and 32 minutes, while third seed Anastasia Potapova eased past Elizabeth Mandlik 6-2 6-0.
Top seed Caroline Garcia cruised into the second round at the Monterrey Open in Mexico on Tuesday, winning 6-3 6-4 over Slovenia's Kaja Juvan.
Third seed Donna Vekic survived an early scare to win by virtue of a walkover at 2-6 5-0 against Lesia Tsurenko who retired for the second straight tournament.
Fourth seed Elise Mertens was too strong for Diana Shnaider 6-0 6-4, while seeds Mayar Sherif and Elisabetta Cocciaretto also progressed.
Sixth seed Katerina Siniakova, who made last week's Mexican Open semi-finals, was eliminated after a controversial call on match point in a third-set tie-break, losing to Kamilla Rakhimova 7-6 (8-6) 2-6 7-6 (7-5).
Last week's Mexican Open champion Camila Giorgi was knocked out 6-4 7-5 by Romanian qualifier Elena-Gabriela Ruse.
The Belgian, ranked 17th in the world, prevailed 6-2 4-6 6-4 over Kristina Mladenovic of France in two hours and 40 minutes to advance in San Jose.
She moves on to face the eighth seed, Yulia Putintseva, who rallied past Ajla Tomljanovic 3-6 7-5 6-3 as the Australian blew numerous chances to pull ahead by converting only two of 16 break-point opportunities.
In the bottom half of the draw, second seed Elena Rybakina remained on track with a 2-6 6-0 6-2 victory over American Claire Liu in a rematch of a second-round meeting at Wimbledon.
Rybakina next meets seventh seed Danielle Collins, a 3-6 6-4 6-3 winner over US countrywoman Sloane Stephens.
Stephens, the 2017 US Open champion, has slipped to number 67 in the world and was playing in her first tournament since Wimbledon as she prepares for a return to Flushing Meadows.
Former world number one and third seed Williams prevailed in a tricky test against Margarita Gasparyan in straight sets in New York on Thursday.
Countrywoman and second seed Kenin contained Canadian teenager Fernandez behind closed doors at Flushing Meadows.
It was not good news for 10th seed Muguruza, who was sent packing by unranked Bulgarian Tsvetana Pironkova.
SERENA WINS THROUGH
Williams continued her quest for a record-equalling 24th grand slam after defeating Russian Gasparyan 6-2 6-4 to set up a showdown with 2017 US Open winner Sloane Stephens.
The 38-year-old Williams hit 27 winners and just 16 unforced errors, an improvement on her numbers in the opening round, under the Arthur Ashe Stadium lights.
Williams, who has not won a slam since the 2017 Australian Open, will next meet Stephens after the American 26th seed eased past Olga Govortsova 6-2 6-2.
KENIN SEES OFF FERNANDEZ
Kenin advanced to the third round of her home slam for the fourth year in a row thanks to a 6-4 6-3 victory over Fernandez.
World number four Kenin did not face a break point in a contest lasting one hour, 21 minutes.
After firing 19 winners and three aces, Kenin will play Ons Jabeur – who took down Kaia Kanepi 7-6 (10-8) 6-0.
MUGURUZA STUNNED
Muguruza's US Open campaign came to an end in the second round, sensationally upstaged 7-5 6-3 by Pironkova, who is playing her first tournament since Wimbledon in 2017.
Australian Open runner-up and two-time slam champion Muguruza was serving for the first set when the Spaniard started to unravel.
Pironkova, who gave birth to a son during her time away from the WTA Tour, took control at the end of a tight first set and never looked back.
"I'm not going to hide, I didn't expect my first tournament to be so good and to play so well. It's welcome! That's why I came back, for these matches and these stages," Pironkova said after winning 93 per cent of her first serves.
AZARENKA ROLLS ON
Former world number one and two-time Australian Open champion Victoria Azarenka topped fifth seed Aryna Sabalenka 6-1 6-3.
A US Open finalist in 2012 and 2013, Azarenka is in fine form after winning the Western & Southern Open last week.
And Azarenka is now just one victory away from her first second-week appearance at Flushing Meadows in five years.
Meanwhile, seventh seed Madison Keys also progressed to the third round.
It took time for Williams to get going on Arthur Ashe Stadium as a mixture of poor timing, particularly on the backhand, and fantastic variety from Stephens saw the 2017 champion take a deserved lead.
But Williams, once again attempting to level Margaret Court's overall record of 24 grand slams, remained calm, upped the ante and, by the time she broke for a 4-2 lead in the second, Stephens never looked like recovering.
The third seed, a six-time champion in New York, won 10 of the final 12 games and can now look ahead to for a fourth-round tie with Maria Sakkari.
Early doors it appeared more likely Williams would be preparing her suitcase as the American great's timing on her groundstrokes was left wanting.
Stephens consistently stretched the play wide with Williams' movement nowhere near its peak and a couple of poor backhands set up a double-break 5-2 lead before the opening set was ruthlessly served out to love.
As has so often been the case, though, Williams shook it off and found another gear, triumphing in a 16-shot rally to break for 4-2 before the errors crept into Stephens' game, which had previously been so clean.
In no time the match was level at a set apiece as the momentum shifted wildly into Williams' favour and, although Stephens valiantly fought off three break points, she made the breakthrough when her opponent went long to open up a 3-1 lead in the decider.
From there it was little more than a training exercise for Williams, who wrapped proceedings up in one hour and 43 minutes when Stephens went long from the baseline.
STATISTICAL BREAKDOWN
Williams [3] bt Stephens [26] 2-6 6-2 6-2
WINNERS/UNFORCED ERRORS
Williams – 29/23
Stephens – 25/18
ACES/DOUBLE FAULTS
Williams – 12/3
Stephens – 0/1
BREAK POINTS WON
Williams – 4/10
Stephens – 2/5
FIRST SERVE PERCENTAGE
Williams – 60
Stephens – 79
PERCENTAGE OF POINTS WON ON FIRST/SECOND SERVE
Williams – 78/39
Stephens – 60/53
TOTAL POINTS
Williams – 81
Stephens – 72
Stephens, who won at Flushing Meadows in 2017, was beaten 5-7 6-2 6-3 in the third round on Friday by three-time major champion Kerber.
The American had defeated outstanding teenager Coco Gauff in her previous match but could not maintain a title challenge in New York.
It was a defeat that prompted a shocking response on social media, Stephens revealed on Saturday.
"I am human," she wrote on her Instagram story. "After last night's match I got [more than 2,000] messages of abuse/anger from people upset by yesterday's result.
"It's so hard to read messages like these, but I'll post a few so you guys can see what it's like after a loss..."
Stephens then shared screenshots of a series of threatening, racist and misogynistic messages aimed in her direction.
She added: "This type of hate is so exhausting and never ending. This isn't talked about enough, but it really freaking sucks...
"I'm happy to have people in my corner who support me. I'm choosing positive vibes over negative ones.
"I choose to show you guys happiness on here, but it's not always smiles and roses."
