The top-ranked Nadal beat Tomas Berdych, 7-6 (3), 6-1, in the early match to leave Djokovic needing only one set to finish second in Group A, and the third-seeded Serb defeated a listless Andy Roddick, 6-2, 6-3.
Nadal will meet Andy Murray in Saturday's opening semifinal as he bids for his first title at the end-of-season tournament. Djokovic plays Roger Federer.
Roddick began his match against Djokovic with an outside chance of reaching the semifinals, but the eighth-ranked American was never in contention and was broken three times in a 65-minute loss.
Nadal, meanwhile, finished Group A with a 3-0 record and appears finally to be getting to grips with the surface at the O2 Arena, having lost all three matches on the same court last year.
It wasn't all plain sailing for Nadal, who lost his cool momentarily and argued furiously with the officials in the first set.
With Nadal trailing 6-5, Berdych's backhand was called out by Brazilian umpire Carlos Bernardes, but Nadal had returned the ball in play. Berdych challenged the call, which confirmed the ball was actually in. The Czech player was then awarded the point.
Nadal was convinced the point should have been replayed, and ranted first at Bernardes and then at the tournament supervisor sitting in the front row of the crowd, to no avail.
Roddick, who had qualified for the eight-man tournament for the eighth straight year, leaves London with an 0-3 record after a surprisingly lackluster performance on Friday.
The 28-year-old American had won his last four matches against Djokovic and engineered a break point in the opening game, only to put a backhand into the net.
Roddick failed to threaten again. A forehand into the net handed Djokovic his first break of the set at 2-1, and Roddick went on to rack up 22 unforced errors as his season ended with a whimper.
"Feel I've been struggling physically on and off for a while now," Roddick said. "I am looking forward to resting for 10 days and then trying to get in shape. It probably came to an end at about the right time."
U.S. women's soccer team no longer a powerhouse as it plays for a World Cup berth
There was a time not too long ago when the U.S. women could roll over opponents even when the Americans were far from at their best.
Those times are clearly gone.
Stunned in regional qualifying, the top-ranked Americans are scrambling for a spot at next year's Women's World Cup — a tournament they've won twice. After beating Italy last weekend in the first leg of a home-and-home playoff, the Americans can advance with a win or a draw in Saturday's finale at Toyota Park in Bridgeview, Ill.
"I think what we're going through is a lot of months of soccer. It's not so much physical fatigue as it is mental," captain Christie Rampone said. "We're not stressing, we're not panicking too much. What we're focused on right now is we're not playing the best soccer [so] let's just get the job done. If we qualify … then we'll worry about fixing the things here and there come January."
The Americans are not exactly a dying dynasty. Their loss to Mexico in the CONCACAF semifinals was their first since the opening game of the Beijing Olympics — where they went on to win the gold medal — and only their second since the 2007 World Cup. They've given up 26 goals in 61 games under Coach Pia Sundhage and have outscored opponents 47-6 this year alone.
But the United States is no longer the juggernaut it was in the 1990s, when Mia Hamm inspired millions of girls all over the world to lace up their cleats.
"All the nations in Europe, the world, have improved," Italy Coach Pietro Ghedin said. "The big gap, it's a little bit smaller. But it is still a gap."
It would be "very difficult" to face the United States at any time, Ghedin said, but Italy's job is made tougher by the loss of forward Melania Gabbiadini, who will be sidelined again with a twisted ankle. Gabbiadini, who had six goals during European qualifying, missed last weekend's game with the ankle injury.
Italy still has Patrizia Panico, who scored 10 goals during European qualifying. The Azzurre went undefeated in winning their qualifying group only to lose to France in the playoffs to determine Europe's first four qualifiers. (Germany automatically qualified as host.) It then beat Ukraine and Switzerland to earn the spot in the playoff against the U.S.
But the United States has won nine of its last 11 games against Italy and is 21-1-2 against European teams under Sundhage.
Golden State Warriors forward David Lee has been cleared to rejoin the team after two elbow operations.
The Warriors said Lee worked out in Oakland on Friday and was examined by the team physician.
He was set to fly to Minneapolis, where the Warriors face the Timberwolves on Saturday. It had not been decided whether Lee would play.
Lee initially had surgery Nov. 12, two days after he cut the inside of his left elbow on the mouth of New York's Wilson Chandler. A fragment of Chandler's tooth stayed in Lee's arm. After Lee's elbow swelled and bled, he needed more surgery.
Hasegawa beats Burgos for WBC featherweight title
Hozumi Hasegawa of Japan beat Juan Carlos Burgos of Mexico by unanimous decision to win the vacant WBC featherweight title in Nagoya, Japan.
The 29-year-old Hasegawa, a former WBC bantamweight champion, improved his record to 29-3 with 12 knockouts. The 22-year-old Burgos dropped to 25-1 with 18 KOs.
Takahiro Aoh of Japan outpointed Vitaly Tajbert of Germany to win the WBC super featherweight title. Aoh improved to 20-2 with one draw. Tajbert dropped to 20-2.
Gypsy's Warning wins Matriarch at Hollywood Park
A Group I winner in her native South Africa, Gypsy's Warning now has a Grade I victory on her resume after her come-from-behind score in the $250,000 Matriarch Friday at Hollywood Park.
The 5-year-old daughter of Mogok and the Royal Chalice mare Gypsy Queen rallied in the center of the turf to defeat pacesetter Wasted Tears and five others.
Owned by Team Valor International and Green Lantern Stables and trained by Graham Motion, Gypsy's Warning earned her second victory in five races in the United States.
Under new rider Joel Rosario, Gypsy's Warning completed the mile in 1:34.01 while winning by 1¼ lengths.
Kicking off Hollywood Park's Turf Festival, which continues Saturday and Sunday, Gypsy's Warning paid $9.80, $4.20 and $3.20.
Wasted Tears finished a half-length in front of Go Forth North.
Racing continues Saturday at 12:30 p.m. The 10 race card includes two more Turf Festival races: the $250,000 Citation Handicap and the $100,000 Generous Stakes.
Court Vision, who won the 2008 Hollywood Derby in his only other local start, is one of 10 scheduled to compete in the Citation, a Grade II at 1 1/16 miles. The Generous is a Grade III for 2-year-olds at one mile. Comma to the Top, the easy winner of the Real Quiet Stakes Nov. 6, heads a field of nine.