If Williams can make that 21 in a row by beating Caroline Wozniacki in Sunday's final, the 32-year-old American will become the first woman since Chris Evert in the 1970s to win three consecutive titles at the tournament.
After Makarova held to 1-all, she went 40 minutes until taking another game. Powered by swift serves and stinging forehands, Williams grabbed nine straight games, including a stretch in which she took 22 of 24 points.
Williams' semifinal was far less dramatic than Friday's earlier match, when Wozniacki's opponent, China's Peng Shuai, retired in the second set because of heat illness and left the court in a wheelchair.
Wozniacki was up a set and a break on an extremely humid afternoon when Peng stumbled to the wall behind the baseline with severe cramping in her legs. Helped off the court, she returned after a 10-minute delay to try to keep playing.
But six points later, Peng collapsed to her knees. Wozniacki walked to the other side of the court to pat her on the back before the Chinese veteran decided she couldn't continue.
Both players were in tears as Peng was taken off, a towel draped over her head.
"It's definitely very difficult," Wozniacki said in an on-the-court interview. "You're out there and you want to battle and want to finish it off properly. I feel sorry for Peng. ... I hope she'll be OK."
This is Wozniacki's first major final since the 2009 US Open, when she lost to Kim Clijsters.
"I have goose bumps right now," she said.
The 10th-seeded Wozniacki won the first set in a tiebreaker and was up 4-3 in the second when Peng, who had appeared in discomfort for some time, began struggling to stand.
Clearly unnerved, Wozniacki then double-faulted to give Peng a break point. But Peng dropped her racket and limped to the back wall, where she tried to stretch her legs.
Players cannot receive treatment during a game or a medical timeout for merely cramping, but they can for heat illness. Tournament director David Brewer said in an interview on CBS that the trainer determined Peng was suffering from heat illness.
While Peng was being evaluated off court, Wozniacki practiced serves for a few minutes before sitting down in her change-over chair. Peng still had difficulty moving when she got back and returned a serve long to erase the break point. But she summoned enough energy to smash back the next serve for a winner and another break point.
That was saved when she meekly hit a forehand wide, except Wozniacki double-faulted again for a third break point. After Peng hit a forehand long, she bent over with her hand to her mouth. And when she tried to return Wozniacki's next serve, she crumpled to the court.
The temperature was in the mid-80s, but the humidity was above 70 percent.
The 39th-ranked Peng hadn't been past the round of 16 at a major tournament before her run at this US Open, when she upset fourth-seeded Agnieszka Radwanska in the second round. Peng had been broken just three times here, with none in her last three matches. On Friday, Wozniacki earned four breaks in 10 service games.
One of those came when Peng tried to serve out the first set at 6-5.
Wozniacki lost the first point of the tiebreaker on her serve, then won the next seven to clinch the set. The streak started with the sort of point that Wozniacki has been constructing all tournament, buttressing her signature defense with some timely offense. She pushed Peng from side to side on a 26-stroke rally, closing it out with an overhead.
Peng broke Wozniacki early in the second set but again couldn't hold in the next game. Wozniacki then broke at love to go up 3-2 as Peng started wincing and clutching at her legs.
Wozniacki made her first Grand Slam final at age 19 here in 2009 and reached No. 1 in the world the next year. But her counterpunching style fell short against other top players, and as her ranking slid, she was most famous as the tennis player who was dating golf star Rory McIlroy.
That ended in very public fashion in late May when McIlroy called off their wedding after the invitations had gone out. Wozniacki lost in the first round at the French Open soon thereafter and was upset in the fourth round at Wimbledon. She had been playing much better since, though, winning her first title in nine months at Istanbul then dropping a pair of three-set matches to the top-ranked Williams.
All the while, she has been training to run November's New York City Marathon. Instead of exhausting and distracting her, the plan seems to have sharpened her game mentally and physically.
Information from The Associated Press was used in this report.