Tennessee Titans running back Henry is a two-time All-Pro and has featured in two Pro Bowls, while he was named the NFL Offensive Player of the Year in 2020 and led the league for rushing yards and touchdowns in 2019 and 2020.
The 28-year-old has now, alongside actor and producer Witherspoon and her husband, the technology investor Jim Toth, joined the ownership group of Nashville SC, who had their inaugural season in MLS in 2020 and sit eighth in the Western Conference with three wins so far this season.
All eight of Nashville's games so far in 2022 have been played on the road, but that will change on Sunday when they welcome the Philadelphia Union to their new stadium, GEODIS Park.
With a capacity of 30,000, it is the largest soccer-specific stadium in the United States or Canada.
"As a kid growing up in Florida, I imagined being a professional sports owner and the opportunity to do that with an MLS club is truly a dream come true," said Henry, who was drafted by the Titans in 2016 and becomes the fourth player in NFL history to own an MLS team.
"My investment in Nashville SC is way more than financial, it's truly an investment in the city of Nashville.
"The chance to be part of a club like Nashville SC, especially after seeing what they are accomplishing in the community, was an opportunity I did not want to miss."
Witherspoon added: "As a Tennessee native, it is thrilling to see how much growth and development has come to our home state.
"One of the things that my whole family is most excited about is Nashville Soccer Club! The opportunity to go as a family and watch a world-class team compete has been such an incredible experience."
Witherspoon is not the first A-list film star to have invested in soccer in the United States, with Natalie Portman having founded Angel City FC, who debuted in the National Women's Soccer League this year.
Tennis greats Billie Jean King and Serena Williams, along with a host of huge stars across sports and entertainment, have a stake in Angel City.
Union took an early lead after Lukas MacNaughton's 16th-minute own goal before Denmark international Uhre bagged a double before half-time.
Uhre added a third in the 56th minute to round out his hat-trick, tapping in Julian Carranza's low ball across goal and put the contest to bed.
Toronto pulled one back through Italy international Lorenzo Insigne in the 66th minute, before Richie Laryea's stoppage-time consolation.
New England reinforced their grip on top spot in the Eastern Conference with a 2-1 home win over Sporting KC, who are last overall.
Giacomo Vrioni netted a first-half brace for the Revs, but Sporting pulled one back in the 50th minute from Johnny Russell, only to be reduced to 10 men when Andreu Fontas was sent off 10 minutes later.
The Revs are ahead of second-placed Cincinnati on goal difference, with Cincy winning 2-1 over Portland Timbers after strikes from Sergio Santos and Brandon Vasquez.
New York City moved up to fourth in the East with a 3-1 home win over Dallas sparked by Santiago Rodriguez's double.
Western Conference leaders St Louis City were denied victory after Michael Barrios' 90th-minute equaliser as they drew 1-1 at Colorado Rapids.
St Louis remain top in the West but only on goal difference from Seattle Sounders who condemned Minnesota United to three straight losses with a 1-0 victory.
Denis Bouanga netted his seventh goal of the MLS season as LAFC drew 1-1 at Nashville, while LA Galaxy snapped their winless start to the campaign with a 2-0 home victory over Austin.
Inter Miami's losing run extended to six in a row, compounding the pressure on boss Phil Neville, as they went down 1-0 at Houston Dynamo.
Real Salt Lake beat San Jose Earthquakes 3-1, Charlotte defeated Columbus Crew 1-0, struggling Montreal edged New York Red Bulls 2-0 and Christian Benteke scored as DC United won 3-1 at Orlando City.
A Maximiliano Urruti double within the opening half-hour put Austin in a commanding position at the interval, but they struggled in the second half, giving up eight shots to three despite 62.3 per cent of possession.
Sebastian Driussi clinched the result for Josh Wolff's side in the 68th minute, though, getting on the end of a flick-on from Nick Lima's long-throw at the back post to head home.
Austin have now gone five games undefeated in the league, bouncing back from Wednesday's elimination at the hands of San Antonio FC in the US Open Cup.
They remain a point ahead of the Los Angeles Galaxy, who scraped a 1-0 win at home to Nashville via Dejan Joveljic's winner in the 86th minute. Real Salt Lake slipped up away to Portland Timbers, playing out a goalless draw.
There were also goalless draws between Sporting KC and Columbus Crew, and Colorado Rapids and Charlotte FC.
They were leapfrogged by FC Dallas, who claimed their fourth win of the season with a 2-1 win over Houston Dynamo.
They left it very late in the Texan derby after Sabastian Ferreira's opener for Dynamo in the 33rd minute, only equalising in the 87th minute through Tsiki Ntsabeleng.
Facundo Quignon claimed the three points for the Toros, lurking unmarked at the back post from a corner to score in the third minute of injury time.
Philadelphia Union remained top of the Eastern Conference despite a 1-1 draw at home to Montreal CF, giving the impetus to Orlando City and New York RB to make up ground on Sunday.
San Jose Earthquakes moved from the bottom of the Western Conference with a shock 4-3 win over the Seattle Sounders. Cristian Espinoza scored the winner for his hat-trick in the fourth minute of injury time via the penalty spot.
In Saturday's other results, Minnesota FC defeated Chicago Fire 3-0, while DC United claimed a 3-2 win over New England Revolution.
Goals in the second half from Carlos Vela and Jose Cifuentes handed LAFC the three points, to put them three points clear of Austin FC, who have a game in hand.
James Igbekeme missed from close range for the Crew in the third minute and with the majority of possession, failed to create anything of substance from that point.
LAFC were able to punish them in transition through Vela in the 62nd minute, darting in behind the defensive line before finishing past Eloy Room.
Cifuentes doubled the margin in the 73rd minute, left with a relatively simple finish after Cristian Arango claimed the ball just outside the penalty area in a comical loss of possession from a Crew goal kick.
The win moves LAFC to 26 points from 13 games but elsewhere in the Western Conference, Nashville SC were unable to move to fourth, twice letting the lead slip in a 2-2 draw with Atlanta United.
In the Eastern Conference, DC United and Toronto FC also played out a 2-2 draw, while Tommy McNamara's spectacular finish in the 89th minute handed the New England Revolution a 3-2 win over Cincinnati.
The bizarre incident occurred in stoppage time with the Red Bulls trailing 2-0 after Yearwood conceded a foul near the sideline, with the Englishman kicking away the ball in frustration.
Yearwood's errant kick cannoned into two young fans in the front few rows at Red Bull Arena, with a boy seen crying afterwards while a young woman seemed dazed. Yearwood immediately realised his error and attempted to apologise to the fans, by climbing into the stands but that effort was not accepted by those close to the shaken-up supporters.
The Red Bulls crowd could be overheard chanting against Yearwood before referee Timothy Ford gave him his marching orders.
The incident capped a poor night for the home side, with goals from Mikael Uhre and Daniel Gazdag clinching the win for Union, who sit top of the Eastern Conference.
Gazdag's goal, which came after Julian Carranza dispossessed Aaron Long, was his 18th of the campaign.
Dallas scored three goals in three minutes as Dallas firmed up their grip on a playoffs spot with a 3-0 road win over Minnesota United.
Michael Boxall netted a 55th-minute own goal before Alan Velasco curled in a right-foot strike less than a minute later.
Two minutes later, Velasco cannoned an effort into the crossbar with Jesus Ferreira glancing home their third after Sebastian Lletget collected the rebound and whipped in a cross.
Franco Fragapane was sent off for Minnesota, who also lost Emanuel Reynoso to a worrying ankle concern.
Cincinnati extended their unbeaten run to seven games and moved into the playoffs spots in the Eastern Conference with a 2-0 home win over Charlotte after goals from Nick Hagglund and Luciano Acosta.
Hany Mukhtar scored a double as Nashville claimed their fourth straight win and moved up to fourth in the west with an impressive 4-0 victory over Austin.
Columbus Crew missed a golden opportunity for three points with a 0-0 draw against struggling Chicago Fire.
