The ex-winger brings the curtain down on a decorated career, which began at Sporting CP, where he would enjoy three separate spells.
Nani's most successful period came during his eight-year stint with Man Utd, with whom he won four Premier League titles, the Champions League and Club World Cup.
He was also part of the Portugal side that won Euro 2016, captaining the side during the final victory over France following Cristiano Ronaldo's early withdrawal through injury.
Nani made 112 international appearances between 2006 and 2017 - making him the Selecao's fifth most-capped player, while he represented them at five major tournaments.
His club career was played across seven different countries - having also turning out for the likes of Fenerbahce, Valencia, Lazio, Orlando City and Melbourne Victory, before finishing his career with a short stint at Primeira Liga side Estrela Amadora.
"The time has come to say goodbye, I have decided to finish my career as a professional player," he posted on his social media channels.
"It's been an amazing ride and I wanted to thank every single person who has helped me and supported me through the highs and lows during a career which lasted over 20 years and gave me so many unforgettable memories.
"Time to turn a new leaf and focus on new goals and dreams."
Tesho Akindele proved the difference for Orlando, with his 60th-minute goal seeing off Montreal in the first knockout fixture in Florida on Saturday.
Following a goalless first half, Akindele pounced on a defensive error on the hour mark – converting an easy tap-in after Clement Diop was unable to deal with Rod Fanni's back pass at Walt Disney Resort.
Nani's Orlando will face either Seattle Sounders or reigning Supporters' Shield champions Los Angeles FC in the quarter-finals.
In Saturday's other last-16 clash, Philadelphia defeated New England Revolution 1-0.
Sergio Santos' 63rd-minute effort saw the Union past Bruce Arena's Revolution.
Santos ran onto a lofted pass from Union team-mate Jamiro Monteiro and finished from an acute angle to send the Union through to the next round.
Next up for Philadelphia are either Sporting Kansas City or Vancouver Whitecaps.
In the first Los Angeles derby fixture of the MLS season, former Manchester United and Real Madrid star Chicharito guided the Galaxy to a 2-1 victory on Saturday.
Chicharito, who attempted just one shot in the loss to Seattle Sounders last time out, the sixth time in 10 MLS starts he has taken fewer than two shots (60 per cent) – he attempted fewer than two shots in just 36.7 per cent of his starts in the five major European leagues – improved his league-best tally to six goals with the 11th-minute opener at Dignity Health Sports Park, where he tucked the ball past Pablo Sisniega.
LAFC restored parity 28 minutes from the end when Diego Rossi equalised following some combination play between team-mates Latif Blessing and Corey Baird.
But the Galaxy walked away with maximum points after Chicharito teed up Jonathan dos Santos for the 79th-minute winner.
The Galaxy are second in the Western Conference, level on points with leaders San Jose Earthquakes, while LAFC are four points off the pace in eighth position.
Orlando City captain Nani stayed hot with another goal in the club's 1-1 draw against New York City.
Ex-United winger and Premier League champion Nani scored another memorable goal seven minutes into the second half, finding the back of the net with a stunning effort from the edge of the penalty area.
Nani's third goal in three games had Orlando on track for maximum points until a 77th-minute penalty via Valentin Castellanos salvaged a draw for the visitors.
"I've been working so hard and been focused on my games," Nani said post-match. "I think this is a reward [for] what you do during the week, the preparation into the games."
New York top the Eastern Conference on seven points, level with New England Revolution but a point clear of Orlando, New York Red Bulls and Nashville.
The Revolution lost 2-0 against Nashville, while the Red Bulls ran out 2-0 winners over Toronto.
Elsewhere, defending champions Columbus Crew defeated DC United 3-1, last season's Supporters' Shield winners Philadelphia Union topped Chicago Fire 2-0, Vancouver Whitecaps beat Montreal Impact by the same scoreline, Dallas and Houston Dynamo drew 1-1, while Colorado Rapids edged Minnesota United 3-2.
Former Manchester United winger Nani had set up Daryl Dike for a 26th-minute opener with a tackle-cum-pass before Silvester van der Water doubled Orlando's lead three minutes later with a cross which eluded everyone.
But the visitors rallied after the break with a double strike inside three minutes, firstly with Antonio Carlos' 52nd-minute own goal.
Minutes later Lucas Zelarayan picked out Derrick Etienne Jr who cushioned a pass into the box for Miguel Berry to equalize.
Orlando grabbed all three points with Dike laying back a pass for Junior Urso to lash home a 69th-minute winner from the edge of the box.
The result moves Orlando above Nashville into second spot in the east with 38 points from 22 games, having gone six games unbeaten in the MLS.
Inter Miami continued their excellent recent form after Brek Shea's 90th-minute winner earned them a 1-0 victory away to Cincinnati.
The result extends Phil Neville's side's unbeaten run to four games and means they have lost only once in their past nine, climbing up to 10th spot in the east.
Dominique Badji also netted a late winner, scoring in the 89th minute to lift the Colorado Rapids into second in the west with a 1-0 victory at San Jose Earthquakes.
Real Salt Lake came from a goal down early to win 3-2 over Dallas, while Vancouver Whitecaps scored twice in the final 20 minutes to beat struggling Austin 2-1.
Orlando had taken the lead in the 10th minute from Benji Michel's cool finish and Andrea Perea doubled their advantage in the 58th minute when he met ex-Manchester United winger Nani's right-flank cross.
Philadelphia found a route back into the game when Kacper Przybylko netted with a first-time 68th-minute strike but they could not find an equaliser.
Union came close when City keeper Pedro Gallese made a fine stop to deny Jack Elliott with Jack McGlynn's effort from the rebound hitting the post.
Orlando, who were winless in their past three games, move up to second in the east on 25 points from 14 games.
Union have now only won one of their past five games and are third in the east with 23 points from five games.
Raul Ruidiaz scored a spectacular long-range goal to lift Seattle Sounders back into top spot overall with a hard-fought 1-0 win at Austin.
Ruidiaz moved into the outright lead for most goals this season with his 11th strike, which came in stunning style.
The Peruvian swooped a loose ball, spotting Austin keeper Brad Stuver off his line and expertly firing in from range for the 67th-minute winner.
Austin thought they had a 77th-minute equaliser which was disallowed by the VAR, while Ruidiaz also had a potential second ruled out for offside.
Seattle, whose 13-game unbeaten run ended on Sunday, are up to 32 points from 15 games atop the Western Conference.
Former Manchester United winger Nani scored his ninth goal of the MLS season as Orlando City missed the chance to close the gap at the top after a 1-1 draw at Cincinnati on Saturday.
Cincinnati, who were winless in their past seven games coming in, opened the scoring in the 42nd minute from Brazilian attacker Brenner.
Nani levelled moments after being brought into the game as a 55th-minute substitute, driving forward and firing in a low left-foot pinpoint shot.
The result means back-to-back draws for Orlando who are second in the Eastern Conference, seven points behind leaders New England.
Third-placed New York City blew an early two-goal lead to draw 2-2 away to Toronto.
Santiago Rodriguez and Ismael Tajouri had put City up 2-0 inside 21 minutes but Toronto netted twice after the break.
Richie Laryea pulled one back in the 49th minute before reigning MVP Alejandro Pozuela equalised in the 55th minute with a tap in.
Portland Timbers beat Real Salt Lake 3-2 in a see-sawing contest with Felipe Mora netting the eventual winner.
Columbus Crew suffered their third straight defeat as Ezequiel Barco netted a double for Atlanta City in a 3-2 win.
Dallas continued their good run of recent form, claiming their third win in four games, with a 2-0 triumph over Austin.
Minnesota United won 2-0 over Houston Dynamo, while Colorado Rapids drew 0-0 with Western Conference leaders Sporting KC.
The Portuguese got on the end of Dutchman Silvester van der Water's 87th-minute cross for the winner which keeps Orlando in touch with Eastern Conference leaders New England.
Atlanta had taken a first-minute lead from Josef Martinez's perfectly placed long-range effort, but Kyle Smith equalised on the stroke of half-time from Nani's corner.
Marcelino Moreno restored United's lead in the 66th minute with a stunning curling strike from outside of the box.
Orlando put together a fine team goal to square the game up in the 79th minute as van der Water headed in Benji Michel's pass.
The Dutch substitute would then provide the pass for Nani's decisive goal, which was his seventh strike of the season.
New York City stayed close behind Orlando in the Eastern Conference with their third consecutive win, a 4-1 victory over Columbus Crew.
City piled on the style, racing to a 2-0 half-time lead after strikes from Valentin Castellanos's early header and Thiago's chip.
Keaton Parks added a third with a deft 51st-minute touch, meaning it was the first time all season Columbus had conceded three goals in a game.
Santiago Rodriguez bundled in from close-range albeit requiring a VAR review, before Pedro Santos' consolation penalty.
LA Galaxy, without Javier Hernandez, cruised past Portland Timbers 4-1 to solidify their grip on third in the west.
Malagasy midfielder Rayan Raveloson pulled off a spectacular overheard volley to open the scoring.
Tesho Akindele scored the fastest goal in club history as Orlando got off to a quick start at home to Jaap Stam's Cincinnati on Saturday.
Akindele found the back of the net after just 33 seconds, surpassing the Orlando record set by Chris Mueller (62 seconds) in April 2018.
Nani doubled the lead in stunning fashion in the 19th minute – the former Manchester United star leaving Yuya Kubo on the floor after cutting to his right foot and then his left as he curled the ball past Przemyslaw Tyton.
After Nani hit the post minutes later and saw his shot saved by Cincinnati goalkeeper Tyton just past the hour mark, Junior Urso sealed the victory with 10 minutes remaining.
Orlando – who remain unbeaten through three games – are third in the Eastern Conference, behind leaders New England Revolution and second-placed New York City.
The Revolution edged Atlanta United 2-1 and New York City defeated reigning Supporters' Shield winners Philadelphia Union 2-0.
The Earthquakes and Dallas, meanwhile, both won 4-1 against DC United and Portland Timbers respectively.
Jackson Yueill's brace and a pair of assists from Cade Cowell fuelled the Earthquakes, who are top of the Western Conference on goal difference but level on points with Real Salt Lake, LA Galaxy and Austin FC.
Dallas showed no mercy at home to the Timbers after Andres Ricaurte and Jader Obrian scored in the opening 13 minutes.
Real Salt Lake came from behind to top Sporting Kansas City 3-1 courtesy of Rubio Rubin's second-half double, while MLS newcomers Austin prevailed 1-0 against Minnesota United.
Elsewhere, New York Red Bulls were 2-0 winners over Chicago Fire, defending champions Columbus Crew were held to a goalless draw by Montreal Impact and Houston Dynamo and Los Angeles FC played out a 1-1 draw.
A last-gasp 1-1 draw against New York Red Bulls was enough for Orlando to secure a place in the MLS Cup play-offs on Sunday.
Orlando were stunned in stoppage time – Brian White's 95th-minute equaliser cancelling out Nani's 56th-minute penalty at Red Bull Arena.
But after Toronto edged Atlanta United 1-0, Orlando were assured of their first trip to the play-offs, having entered the league in 2015.
"We've put ourselves in a good position," Orlando forward Daryl Dike said. "Obviously we just made the play-offs today, but I think we're going to carry on. The goal wasn't just playoffs. We're not done now. We just keep going and keep going.
"We want three points every single game and we want to finish the highest in the table. That's the main goal."
Orlando – fourth in the Eastern Conference – are in the midst of a club-record 12-game unbeaten streak, per Stats Perform.
The Crew's 3-1 win over New York City, coupled with Toronto's triumph, sent the team back to the play-offs after missing out last season.
Columbus also snapped a four-match winless streak to move third in the east, two points ahead of Orlando and a point behind second-placed Philadelphia Union.
Elsewhere, LA Galaxy ended a six-game losing skid by topping Vancouver Whitecaps 1-0 thanks to substitute Kai Koreniuk's late winner.
Koreniuk became the first substitute to score for the Galaxy this season – the Los Angeles club were the only team without a goal from a substitute in 2020.
Los Angeles FC's Christian Torres (16 years, six months and three days) became the youngest player to score in MLS since Sporting Kansas City's Gianluca Busio (16 years, four months and 20 days) in 2018, according to Stats Perform.
Torres' last-gasp equaliser earned LAFC a 1-1 draw at Western Conference high-flyers Portland Timbers.
Seattle Sounders drew 0-0 with San Jose Earthquakes, Houston Dynamo played out a 2-2 draw against Minnesota United and DC United beat FC Cincinnati 2-1.
Johnny Russell scored a goal and assisted two others as Sporting KC routed Minnesota at Children's Mercy Park on Wednesday.
Russell converted a penalty as part of a three-goal first half, with Khiry Shelton and Daniel Salloi also on target against the visitors.
Cameron Duke added a fourth goal seven minutes into the second half as Sporting KC found the back of the net in their 28th consecutive regular-season home game dating back to August 2019 – the longest active streak in MLS.
Sporting KC are a point clear in the west, though second-placed Seattle Sounders have played two games less, while Minnesota are two points outside the play-off positions.
San Jose Earthquakes star Javier Lopez scored a hat-trick, but Real Salt Lake still prevailed 4-3 in a wild clash.
Lopez opened the scoring in the 26th minute and completed his treble in the second half, however, RSL emerged victorious thanks to Rubio Rubin's brace.
The result snapped a five-match away losing streak for RSL, who ended San Jose's run of three consecutive wins over their rivals in MLS – a run that had equalled the longest streak by either team in history.
Elsewhere, former Manchester United and Real Madrid striker Javier 'Chicharito' Hernandez salvaged a 1-1 draw for LA Galaxy against Houston Dynamo.
Another ex-United star, Nani, was sent off in the first half as Orlando City were beaten 4-2 by Montreal, Ola Kamara's opening-half hat-trick lifted DC United past Chicago Fire 3-0, Atlanta United were 4-0 winners against FC Cincinnati courtesy of a Josef Martinez double, Los Angeles FC edged Austin 2-1 and 10-man Portland Timbers drew 2-2 with Colorado Rapids.
The former Manchester United forward joined Orlando in 2019, having left Serie A club Lazio.
Nani led the club to their first postseason appearances, while Orlando also reached the final of the MLS Is Back Tournament in 2020.
The 35-year-old scored 12 goals in his first season with the Lions, a further nine in 2020 and 10 this season as Orlando lost in the first round of the playoffs, going down 3-1 to Nashville SC.
He explained it was not his decision to leave, but rather Orlando choosing not to extend his contract.
In a statement posted to his official social media channels, Nani said: "All good things must come to an end. After three amazing seasons, full of great moments, new friendships and sporting success, I am leaving Orlando City.
"Orlando is a city I can call home, with great people and fantastic supporters, but my contract has ended and there was a decision by the club not to extend it.
"It was an honour captaining the club for its first ever playoff appearances and reaching the final of the MLS Is Back Tournament.
"I shall never forget how the fans and community supported me and my family ever since the moment we arrived in Florida. You will have in me a friend and a fan for the future. I wish you all the best."
Portuguese winger Nani has experienced derbies in some of the world's great football cities, having played for Sporting CP, Manchester United, Lazio and Fenerbahce during an illustrious career.
Now an A-League derby awaits the 35-year-old, and he says the occasion will be comparable to his previous experiences of gunning for local bragging rights.
"A derby is a derby. You need to take it the way it is, you need to win," Nani said.
"Derbies are there to win, not to lose, because if you lose, it is the worst day of your life. You cannot go out. I don't feel in the mood to walk around, and you know you feel the shame.
"This is a moment of pride, so you want to give your fans a beautiful night, special feelings, and make them feel we are the best in the country."
Nani said hosts Victory will need to put in an almighty effort to earn all three points in front of a sell-out crowd at AAMI Park.
"We know it's a tough game," he said. "They are a strong opponent as well, so to win we need to give everything we've got and let's wait for the game and see what we can do."
Victory began the season with a 3-2 win over Sydney FC, before falling 1-0 to Western City Wanderers last week.
Last season saw Victory finish one point behind their neighbours, who topped the table in the regular season. Melbourne City then went on to lose to Western United in the Grand Final.
Melbourne City have begun this campaign with two wins, an early indication they should be challengers again.
Nani sees Victory as underdogs this weekend, saying Melbourne City "have a fantastic squad".
"I think probably they've been showing they're better than us on the field, the way they've been performing," Nani said. "So, it will be very tough for us. We need to be a compact team, we need to work very hard, and then try our best to beat them."
At the age of 35, Nani says he is putting in the hours to get in the best possible shape for his latest career challenge in Australia.
Asked if he might produce one of his famous backflips should he grab a derby goal, Nani said: "Yeah, why not? Let's see. I let the environment and the moment make the decision. So, what comes in the brain, we will do."
Orlando came from behind at the Walt Disney World Resort in Florida to grab three points in the Group A clash, in the first MLS outing since the season was suspended in March due to the coronavirus pandemic.
Nani had set up Chris Mueller's equaliser to cancel out Juan Agudelo's opener, before the former Manchester United attacker put away a 97th-minute winner.
It came after players gathered pre-game, kneeling and raising their fists in a show of solidarity with the Black Lives Matter movement.
Inter Miami opened the scoring early in the second half after a fine team move, Agudelo tapping in a Victor Ulloa cross.
Andres Reyes was taken off on a stretcher before the hour-mark after a frightening injury which saw the Inter Miami defender struck on the throat.
Orlando drew level with 20 minutes remaining, Mueller getting on the end of a lovely cross from Nani.
Just as it looked like the teams were set to share the spoils, Nani tucked away a dramatic winner for Orlando.
Former Manchester United star Nani scored twice in the first half to help Orlando set up a showdown with Portland Timbers in Tuesday's showpiece.
Minnesota's Mason Toye reduced the deficit with seven minutes remaining, but Benji Michel's 96th-minute effort sealed Orlando's progression in Florida.
Nani put Orlando ahead after 36 minutes at the Walt Disney World Resort, where the Euro 2016, four-time Premier League and 2008 Champions League winner broke the deadlock.
Robin Jansson played a ball over the top to Nani, who controlled brilliantly before poking the ball past Minnesota goalkeeper Tyler Miller on Thursday.
Nani then produced a moment of magic to double the lead six minutes later, the Portugal winger collecting the ball on the edge of the area, drifting onto his right foot and curling a shot past Miller.
Minnesota's first shot on goal did not come until the 75th minute – Raheem Edwards' free-kick forcing Pedro Gallese into a fine save.
Kevin Molino supplied his third assist to Toye as Minnesota kept their hopes alive with time running out, however, substitute Michel struck in the sixth minute of stoppage time to put the result beyond doubt.
The comfortable win moved the Lions clear of Philadelphia to sit alone in second place behind New England Revolution in Major League Soccer's Eastern Conference.
Nani opened the scoring from the spot in the seventh minute and the Orlando native Michel followed with his first goal of the season after 16 minutes.
The USA international Dike put the game out of reach, netting in the 31st and 49th minutes with Nani assisting on both goals.
Dike was making his first start since returning to Orlando City from a loan to Barnsley, where the 21-year-old scored nine goals in 22 appearances in all competition for the Championship side after his move during the January transfer window.
While Dike departed after 71 minutes, Michel played the entire match for the first time this season and closed the scoring in the 90th minute.
Monday's draw was enough for Orlando to win the group ahead of Philadelphia due to their superior goal difference after both teams finished on seven points from three matches.
Ilsinho came off the bench to put the Union ahead in the 68th minute at Walt Disney Resort in Florida, where his effort from a difficult angle broke the deadlock.
But Orlando hit back just two minutes later through Mauricio Pereyra after he got on the end of Nani's cross.
New York City had defeated Inter Miami 1-0 earlier in the day to eliminate David Beckham's expansion franchise in Group A.
Inter Miami are yet to win a match since entering the league at the start of the 2020 season.
Orlando, who opened their 2021 season with a goalless draw against Atlanta United, had not gone two consecutive games without scoring since August 2019 and they avoided doing so thanks to former Manchester United star Nani.
Gianluca Busio put Sporting KC ahead on the stroke of half-time – Orlando goalkeeper Pedro Gallese's pass picked off by Daniel Salloi, who teed up his team-mate.
Sporting KC won their final three regular-season home games in 2020 – the last visiting side to take a regular-season point in Kansas City were Orlando on September 23.
A cheeky backheel from Nani rescued a point for visiting Orlando with 11 minutes remaining at Children's Mercy Park, where the goal had initially been ruled offside before a video review.
Both teams had goals ruled out for offside in the first half – Nicolas Isimat-Mirin's rebound and Benji Michel's effort.
